Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free..Melanoma..Jim Breitfeller

Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free

Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free Thanks to Clinical Trial Conducted at St. Luke’s

Cancer Expert Lee B. Riley, MD, PhD Served as Co-Investigator and Co-Author in the Phase III Melanoma Vaccine Trial for Patients with Advanced Disease

Suzanne Lapierre-Roman of Allentown was diagnosed with metastatic melanoma at age 29 in July of 2005. The news came as a complete surprise. While pregnant with her fourth child, Suzanne was experiencing pain thought to be caused by her gallbladder, and soon after delivery, had it removed. Test results that came back showed she had cancer – advanced melanoma. “It was a shock,” she says. “At the time, I didn’t even know what melanoma was.”

Suzanne was first seen at a number of university hospitals in Philadelphia and then a local hospital. “I wasn’t given much hope,” she says. “I was told to go on chemotherapy. Then, I heard about Dr. Lee Riley at St. Luke’s. He tested me to see if I would qualify for a melanoma clinical trial. I went on in October 2005.”

The treatment, formulated by National Cancer Institute (NCI) investigators, involves the use of a potent designer peptide vaccine gp100:209-217 (210M) which mimics the antigen that sits on the surface of a patient’s own tumor cells. On its own, the peptide shows little activity. However, in this trial, the vaccine was given in combination with the FDA-approved inpatient therapy for melanoma, High-Dose IL-2, made from a natural protein produced by the body.Dr. Riley, Medical Director of St. Luke’s Cancer Center, served as a co-author and a clinical investigator for the randomized study. St. Luke’s Cancer Center in Bethlehem was the only site in Pennsylvania to participate in the trial and was a major contributor of study participants, including Suzanne. Dr. Riley joined on as an investigator in the study in 2002. The promising results of the trial were presented at the June 2009 meeting of the American Society of Clinical Oncology in Orlando, Florida.

It’s been nearly four years since Suzanne went on the trial and today she is totally disease-free. “Dr. Riley was the only one who gave me hope,” she says. “He told me, ‘When this treatment works, it’s a home run.’ Well, I got my home run. Today, I don’t have any signs of the disease. Dr. Riley is just awesome; I owe him my life.”

“Suzanne’s great results are typical for someone who responds to IL-2, and there is a very good chance she will not have a recurrence. This study suggests that, in the future, more than twice as many people should respond the way Suzanne has,” says Dr. Riley.

Dr. Riley stresses the significance of this study. “The trial has demonstrated for the first time that, a vaccine can improve the outcome of patients with the most advanced stage of melanoma (stage IV). This is a major advance for cancer vaccine research and should stimulate additional cancer vaccine studies.”

More about the study

One hundred and eighty-five patients were enrolled in the study in 21 states from 2000 to 2007. The majority of patients in this study were between the ages of 31 and 60 and had advanced disease. All of the patients were heavily pretreated with surgery and, in some cases, patients had also undergone prior chemotherapy, radiation therapy, or immunotherapy including IL-2.

Study participants received two to four vaccine injections every three weeks. The study showed that those who received the vaccine with high-dose IL-2 had a significant response rate, 22.1 percent compared to 9.7 percent who just received the high-dose IL-2. The overall survival for those receiving the vaccine with IL-2 was 17.6 months compared to 12.8 months (p=0.084).

“The vaccine induces anti-tumor T-cells and the IL-2 stimulates the T-cells to grow and divide,” says Dr. Riley. “T-cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity.”

Now that the study is over, the trial’s investigators are evaluating ways to move it forward so that others with advanced melanoma may also benefit.

Source:http://wellspringhealthandstyle.com/2009/08/20/woman-diagnosed-with-advanced-melanoma-in-2005-remains-disease-free/

The use of a potent designer peptide vaccine gp100:209-217 (210M) which mimics the antigen that sits on the surface of a patient’s own tumor cells. It is used as the Antigen, for the Antigen Presenting Cell (APC)





Take Care,

Jimmy B

PeervVew exchange on Melanoma..Jim Breitfeller

http://www.peerviewpress.com/exploring-new-directions-melanoma-treatment-focus-emerging-immunotherapeutic-approaches

Exploring New Directions in Melanoma Treatment: Focus on Emerging Immunotherapeutic Approaches



Take Care,

Jimmy B

Is Triple Therapy more effective than Single Agent Therapy? Melanoma..Jim Breitfeller

Is Triple Therapy more effective than Single Agent Therapy?

Base on my knowledge there are at least five things you need to accomplish before an immune response can be generated:

1. You need the correct antigen to be presented by the (APC) Antigen presenting cell at the TCR T Cell receptor
2. You need to Activate the CD-4 + T-cell
3. You need to co-stimulate the CD28 receptor
4. You need to suppress the Treg cells
5. You need to a growth factor (IL-2) to grow your army of Cytotoxic Cells

Once activated, you need all the players to help orchestrate the immune response. This can not be done by single agent alone. The immune response has checks and balances that it must pass through. It is like opening a deposit box at the bank. You need the master key to open the first gate. Then you need two different keys to gain access to the deposit box. Plus there is a sequence of events that must be followed to gain access. If you only have one key, you will fail to open the box.

Each Drug company has a key to solving the problem. In order to get the tumor specific response the drug companies must work together.




Take Care,

Jimmy B

I am Not going to tender my Shares of Medarex to Bristol Meyer Squibb. Melanoma..Jim Breitfeller

I am Not going to Tender my Shares of Medarex to Bristol-Meyer Squibb. BMY low balled the tender and Medarex would be better off as a separate company. Here why.

Therapeutic Monoclonal Antibody Production Is More Profitable Than Small Molecule Drugs

New study has suggested that therapeutics based on monoclonal antibodies (mAbs) are fare more likely to be commercially successful than their small molecule predecessors. According to a study completed by // consultancy Propagate Pharma, about half the mAbs launched so fare appear to be profitable. That means mAbs are recouping more in revenues than their estimated $1 billion to $1.8 billion cost of development and marketing. By comparison, the study estimates that only 30% of conventional small molecule drug launches ever recover their costs. Drug is likely to be profitable if peak revenues pass the $300 million mark. So far, of the 17 mAbs launched in the US, eight have achieved this benchmark. And of these, four have become blockbusters earning over a billion dollars a year.

Of 57 mAbs launched so far, 16 have become blockbusters, 14 have at least recouped their costs, and the other 27 are either question marks or failures. The high success rate of biotherapeutics is due to low levels of competition in the markets they address, says Jo Collett, author of the Propagate study. There are signs that the tail end of a biotherapeutics products life cycle might be more profitable than that of a small molecule drug. However, this high level of success may be difficult to sustain as competition increases, especially in the cancer market, says Propagate’s Collett. “It’s not going to be quite as easy as it was for the pioneers,” she prophesies.

There are more than 150 mAbs in development worldwide, over 100 of which are in phase 2 or phase 3 trials. Nearly 40% of these are in the oncology field; 18 are in development for breast cancer alone. Collett predicts that companies launching the next generation of mAb therapeutics will have to be more commercially acute with a better understanding of their products positioning that the pioneers of the field were. Although there is respectable data showing that obtaining regulatory approval tends to be easier for antibodies than for other drug classes, he warns it is too early to make firm predictions. “The mid and longer term future may look quite different in terms of competitive threats, so past performance is not necessarily a guide”.

Source: Nature Biotechnlogy.




Date:10/8/2005


http://www.bio-medicine.org/medicine-news/Therapeutic-Monoclonal-Antibody-Production-Is-More-Profitable-Than-Small-Molecule-Drugs-5161-2/



Take Care,

Jimmy B

15. Standards of Integrity Removed from Medarex website..Melanoma..Jim Breitfeller

15. Standards of IntegrityMedarex maintains Standards of Integrity that apply to Directors, Senior Management and all other employees of Medarex. Medarex’s Standards ofIntegrity may be found on Medarex’s website

at:www.medarex.com/Investor/Corporate.htm.The page you are looking does not exist. It may have been removed, its name may have been changed, it may be under construction, or it may be temporarily unavailable. Try using the menus on the left side of the page to find what you are looking for. If you entered in a URL, please check to make sure you typed the address correctly.


What are they Hiding!!!!!!!!!!


Take Care,

Jimmy B

Bristol-Meyer Squibb is Stealing the Pearl Necklace!!!Monoclonal Antibodies FDA approval over the last 10 years..Melanoma..Jim Breitfeller

Monoclonal antibodies used to treat cancer MAb Name
Trade Name
Used to Treat:
Approved in:

Rituximab
Rituxan
Non-Hodgkin lymphoma
1997

Trastuzumab
Herceptin
Breast cancer
1998

Gemtuzumab ozogamicin*
Mylotarg
Acute myelogenous leukemia (AML)
2000

Alemtuzumab
Campath
Chronic lymphocytic leukemia (CLL)
2001

Ibritumomab tiuxetan*
Zevalin
Non-Hodgkin lymphoma
2002

Tositumomab*
Bexxar
Non-Hodgkin lymphoma
2003

Cetuximab
Erbitux
Colorectal cancer
Head & neck cancers
2004
2006

Bevacizumab
Avastin
Colorectal cancer
Non-small cell lung cancer
Advanced breast cancer
2004
2006
2008

Panitumumab
Vectibix
Colorectal cancer
2006



*conjugated monoclonal antibodies

Two types of monoclonal antibodies are used in cancer treatments:

Naked monoclonal antibodies are those without any drug or radioactive material attached to them.
Conjugated monoclonal antibodies are those joined to a chemotherapy drug, radioactive particle, or a toxin (a substance that poisons cells).

http://www.cancer.org/docroot/ETO/conten...

Think what Our 40+ Antibodies in the pipeline of the Medarex Company are worth.

We have been sold out by Pien and Company!!!!

Bristol-Meyer Squibb is stealing the Pear Necklace from the Medarex Shareholders.

The Boards of Both Companies should be Investigated along with the CEO's

Take Care,

Jimmy B

Is Medarex and Bristol-Meyer Squibb in Collusion With this Tender Offer??..Melanoma..Jim Breitfeller

"Our opinion does not address the underlying business decision of the Company to engage in the Transactions, or the
relative merits of the Transactions as compared to any strategic alternatives that may be available to the Company. We
were not requested to solicit, and did not solicit, interest from other parties with respect to an acquisition of or other
business combination with the Company. This opinion addresses only the fairness froma financial point of view, as of the
date hereof, of the $16.00 per Share in cash to be paid to the holders (other than Bristol and its affiliates) of Shares
pursuant to the Agreement.We do not express any view on, and our opinion does not address, any other term or aspect of
the Agreement or Transactions, including, without limitation, the fairness of the Transactions to, or any consideration
received in connection therewith by, the holders of any other class of securities, creditors, or other constituencies of the
Company; nor as to the fairness of the amount or nature of any compensation to be paid or payable to any of the officers,
directors or employees of the Company, or class of such persons in connection with the Transactions, whether relative to
the $16.00 per Share in cash to be paid to the holders (other than Bristol and its affiliates) of Shares pursuant to the
Agreement or otherwise. Our opinion is necessarily based on economic, monetary, market and other conditions as in
effect on, and the information made available to us as of, the date hereof and we assume no responsibility for updating,
revising or reaffirming this opinion based on circumstances, developments or events occurring after the date hereof. Our
advisory services and the opinion expressed herein are provided for the information and assistance of the Board of
Directors of the Company in connection with its consideration of the Transactions and such opinion does not constitute a
II-2
recommendation as towhether or not any holder of Shares should tender such Shares in connectionwith the Tender Offer
or how any holder of Shares should vote with respect to the Merger or any other matter. This opinion has been approved
by a fairness committee of Goldman, Sachs & Co.
Based upon and subject to the foregoing, it is our opinion that, as of the date hereof, the $16.00 per Share in
cash to be paid to the holders (other than Bristol and its affiliates) of Shares pursuant to the Agreement is fair from a
financial point of view to such holders."


Very truly yours,
/s/ Goldman, Sachs & Co.
(GOLDMAN, SACHS & CO.)













BMY is just pay the same price as before the Financial downturn. Shareholders are getting ripped off!!!!

What about Fiduciary Duty on the part of Medarex?

http://www.medarex.com/Investor/documents/Medarex_14D-9.pdf
Goldman Sachs' Letter to MEDX Board of Directors (BOD) OPENLY Acknowledges that MEDX BOD Failed to Perform Its Fiduciary Responsibilities....


> STRATEGIC ALTERNATIVES NOT CONSIDERED......
--->> "Our opinion does not address the underlying business decision of the Company to engage in the Transactions, or the relative merits of the Transactions as compared to any strategic alternatives that may be available to the Company. "

> MEDX Board DID NOT REQUEST Solicitation of Other Companies......
--->> "We [Goldman Sachs] were not requested to solicit, and did not solicit, interest from other parties with respect to an acquisition of or other business combination with the Company."


Here, as I see it, Goldman Sachs openly acknowledges that the MEDX BOD did not perform its fiduciary responsibility, because:

1). It did NOT ASK GS to consider... "any strategic alternatives that may be available to the Company."

2). The MEDX BOD did NOT ASK GS... "to solicit, and did not solicit, interest from other parties with respect to an acquisition of or other business combination with the Company."

I think that GS stated these two points in their letter to the MEDX BOD, because they knew that the MEDX BOD did perform their Fiduciary Responsibilities to the shareholders, and did NOT want to be sued.

I think the MEDX BOD has utterly and completely FAILED to perform its FIDUCIARY RESPONSIBILITY to the shareholders of MEDX, and that Goldman Sachs' letter CLEARLY DEMONSTRATES THIS AS A FACT.




Take Care,

Jimmy B

Medarex is Giving away the Company without it's Shareholders Consent at a Fireside Sale to Bristol-Meyer Squibb of 50 % off! Melanoma Jim Breitfeller

Headline Pfizer's melanoma disappointment compounds Medarex misery

Source EP Vantage

Company Medarex

Related: Bristol-Myers Squibb, Pfizer

Date April 02, 2008

The termination of a phase III trial of tremelimumab in melanoma, after interim data suggested the drug was no better than standard chemotherapy, could mean Pfizer has lost one its most promising pipeline products.
While the company is not abandoning the antibody, which is in trials for a range of solid tumours, the prognosis is not good, and is the last thing Pfizer needs as it attempts to drive through new products ahead of the looming loss of Lipitor. For Medarex, the news is an even bigger blow, because it makes potential future royalty payments look more uncertain, and adds to concerns around a similar antibody the biotechnology firm is developing with Bristol-Myers Squibb.
Tremelimumab, or CP-675,206, is an anti-CTLA4 antibody which targets a molecule found on the surface of T-cells, and has been shown to diminish the immune response to tumours. By using a human antibody to block the activity of CTLA-4, immune systems may attack tumours more strongly.
There are two anti-CTLA4 MAb’s under development, tremelimumab and ipilimumab, both in final stage trials for melanoma. The Pfizer drug was developed using technology similar to Medarex’s, hence the royalties due on future sales. The latter, also known as MDX-010, was developed by the biotechnology group, and is being progressed under the alliance with Bristol-Myers Squibb.
The consensus net present value of MDX-010 to Medarex is $1.23bn, according to EvaluatePharma’s NPV Analyzer, which represents just over a third of the total value of the group’s pipeline. CP-675,206 is valued at $547m, accounting for just under a fifth, meaning half of the company’s pipeline value is tied up in the success of anti-CTLA4 MAbs.
Medarex shares were trading 15% lower, at $7.88, in early trade.

Second most important

Pfizer shares also opened weaker, down 1%. The consensus NPV of the product is $2.29bn, representing 2% of the company’s share price. That makes it the second most important pipeline project, after axitinib.
Analysts had penciled in sales of $499m by 2012, and were anticipating launch this year. The product is phase II trials in non-small cell lung cancer, colorectal and breast cancers, among others.
Melanoma would be a big opportunity for both CP-675,206 and MDX-010, because the cancer represents a significant unmet medical need. The main drugs used to fight the disease are the interferon alphas, sales of which are in decline as newer, more effective products have been developed for other tumour types, with melanoma remaining hard to treat.
If the antibodies fail to make the grade, the indication will lose two its most promising looking new candidates.

Diminishing hopes

Hopes that the anti-CTLA4 MAbs would prove to be a significant new treatment options were lowered when Bristol-Myers and Medarex released mixed results from three registration phase III trials of ipilimumab in December. One study did not meet the primary endpoint, although the companies have stressed that response rates across the trials were positive.
MDX-010 is due to be filed with the FDA in the first half of the year, and Medarex has expressed confidence that the regulator will approve the drug on the data. Sales forecasts commence in 2008, given the fast track status the drug has been granted, but confidence in straight-off approval has diminished, with many analysts believing further trials will be required.
A sign that Bristol-Myers is also less than confident came in a December slide show given by the company, which showed sales of MDX-010 starting in 2010.
Consensus for 2012 sales sits at $389m recorded by Bristol-Myers. A key event for defining the potential of the drug will come when full data from the three phase III trials is presented at this year’s ASCO conference at the end of May.
With today’s set back, that presentation takes on even greater importance for the biotechnology group. Its shares fell 21% when the news on MDX-010 was announced in December, and aside from a recent small rally, have been falling since.
With the stock now trading at three-year lows, significant progress with the remainder of its pipeline is needed to restore confidence.

This content is written, edited and published by EP Vantage and is distributed by EvaluatePharma Ltd. All queries regarding the content should be directed to: news@epvantage.com
EP Vantage is a unique, forward-looking, news analysis service tailored to the needs of pharma and finance professionals. EP Vantage focuses on the events that will define the future of companies, products and therapy areas, with detailed financial analysis of events in real-time, including regulatory decisions, product approvals, licensing deals, patent decisions, M&A.
Drawing on EvaluatePharma, an industry-leading database of actual and forecast product sales and financials, EP Vantage gives readers the insight to make value-enhancing decisions.



Source: EvaluatePharma®
Source:
http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=10530&componentID=1002#&&_ViewArgs=%7b%22_EntityType%22%3a0%2c%22_Parameters%22%3a%7b%22_ContextData%22%3a%22%7b%5c%22isEPVantage%5c%22%3atrue%2c%5c%22percentage%5c%22%3a-1%2c%5c%22searchWords%5c%22%3a%5c%22%5c%22%2c%5c%22sectionID%5c%22%3a%5c%22%5c%22%2c%5c%22storyID%5c%22%3a%5c%22152431%5c%22%7d%22%7d%2c%22_Type%22%3a1%7d


Based on this information plus 1.5 bn for the othe 39 drugs in the pipeline plus 1.23 for mdx-010 and 2.29 for Tremelimumab, or CP-675,206 equals 5.02 bn

Lets do the math 2.4 bn/16per share = 5.02 bn/X X= 33.5 dollars per share

BMY got a half off deal.


Show us the $$$$$$$$$$$!!!!!!!!!!

Medarex List of products in the pipline!!!! 14-Aug-09 10:13 pm
Product Count
Medarex
Marketed 3
R&D 62
Suspended in R&D 1
Abandoned in R&D 42
Disposed in R&D 1
Total (Medarex) 109

DEPTH COMPETITIVE INTELLIGENCE AVAILABLE ON

Product Generic Name
Medarex
aB7H4
-
ADC Research Program
-
AFP-VAC
-
ALT-212
-
AMG 714
-
Amgen Antibody-1
-
Amgen Antibody-2
-
Amgen Antibody-3
-
Amgen Antibody-4
-
Amgen Antibody-5
-
Anti-bacterial MAb
-
Anti-CD70 MAb-MGBA conjugate
-
Anti-Cripto-1 MAb
-
Anti-CTLA-4 project
-
Anti-SDF-1 MAb
-
aPtk7
-
ARIUS/Medarex Cancer Research Project
-
AutoImmune MAb Collaboration
-
Avalon Cancer Antibody Collaboration
-
BMS-66513
-
Cancer antibody collaboration
-
Cancer MAb Project
-
Cancer Research Project
-
CDX-110
-
CDX-1307
-
CDX-1401
-
CDX-2101 (inc. Ribi-529 adjuvant)
hepatitis B vaccine

CDX-2301
anthrax vaccine

CDX-2401
-
CDX-2410
-
CDX-S03
-
CNTO 95
intetumumab

COL-VAC
-
Compugen antibody collaboration
-
CP-675,206
tremelimumab

DTS-201
-
Duocarmycin B2
-
Eos/Medarex/Biosite Cancer MAb
-
Euroscreen MAb collaboration
-
FG-3019
-
Fully-Human RSV MAbs
-
Graft versus Host Disease Project
-
GVHD-TOX
-
Haematological cancer MAb collaboration
-
HGS-TR2J
-
HuMax-CD4
zanolimumab

HuMax-Inflam (MDX-018)
-
IL-13 Antibody
-
Ilaris
canakinumab

IMC-18F1
-
IMC-3G3
-
Immunology MAb collaboration
-
Infectious Disease Research Project
-
Ipilimumab
ipilimumab

KW-2189
pibrozelesin

LOR-A04
-
Lung Cancer MAb
-
MAb Research Project
-
MAGE3
-
MDX 1097
-
MDX-060
iratumumab

MDX-066
-
MDX-067
-
MDX-070
-
MDX-11
-
MDX-1100
-
MDX-1105
-
MDX-1110
-
MDX-1185
-
MDX-1203
-
MDX-1204
-
MDX-1338
-
MDX-1342
-
MDX-1388
-
MDX-1401
-
MDX-1411
-
MDX-1414
-
MDX-214
-
MDX-22
-
MDX-220
-
MDX-240
-
MDX-33
-
MDX-44
-
MDX-447
-
MDX-RA
-
Medarex/Pfizer UltiMAb Antibody
-
Medarex/Raven MAb
-
MEDI-545
sifalimumab

MEDI-546
-
MelanA
-
MEL-VAC
-
NI-0401
-
Novartis Antibody 2
-
NY-ESO-1
-
OGeS cancer antibody collaboration
-
ONO-4538 / MDX-1106
-
Organon/Medarex MAb
-
Osidem
-
Ovarian Cancer MAb
-
PSA-VAC
-
Resiquimod (inc. CDX-1307 adjuvant)
-
SARS MAb
-
Second-generation MDX-070 toxin conjugate
-
Simponi
golimumab

Stelara
ustekinumab

Transcobalamin MAb
-
Valortim
-
VAP-1 Antibody Program
-
Vitamin B12 Receptor Blocking MAb

Take Care,

Jimmy B

ew Method Takes Aim at Aggressive Cancer Cells..Melanoma ..Jim Breitfeller

Released: Mon 10-Aug-2009, 11:00 ET

Newswise — A multi-institutional team of Boston-area researchers has discovered a chemical that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.

These cells, known as cancer stem cells, are thought to enable cancers to spread — and to reemerge after seemingly successful treatment. Although further work is needed to determine whether this specific chemical holds therapeutic promise for humans, the study shows that it is possible to find chemicals that selectively kill cancer stem cells. The scientists’ findings appear in the August 13 advance online issue of Cell.

“Evidence is accumulating rapidly that cancer stem cells are responsible for the aggressive powers of many tumors,” says Robert Weinberg, a Member of Whitehead Institute for Biomedical Research and one of the authors of the study. “The ability to generate such cells in the laboratory, together with the powerful techniques available at the Broad Institute, made it possible to identify this chemical. There surely will be dozens of others with similar properties found over the next several years.”

“Many therapies kill the bulk of a tumor only to see it regrow,” says Eric Lander, Director of the Broad Institute of MIT and Harvard, and an author of the Cell paper. “This raises the prospect of new kinds of anti-cancer therapies.”

An emerging idea in cancer biology is that tumors (breast, prostate, colon, lung, etc.) harbor a group of cells with the unique ability to regenerate cancers. In addition to promoting tumor growth, these so-called cancer stem cells are largely resistant to current cancer therapies. If it were possible to identify chemicals that selectively kill cancer stem cells, such chemicals might become critical candidates for future drug development.

However, researchers have struggled to study cancer stem cells directly in the laboratory. The cells’ relative scarcity compared to other tumor cells, combined with a tendency to lose their stem cell-like properties when grown outside of the body, have severely limited the amount of material available for analysis.

To overcome these hurdles, Broad and Whitehead Institute researchers drew upon recent findings from Weinberg and his colleagues that suggested a way to generate in the laboratory large numbers of cancer cells with stem cell-like qualities. The technique works by coaxing adult cells to undergo a critical change (known as an “epithelial-to-mesenchymal transition”) that alters their shape and motility. At the same time, the cells also adopt similar properties as stem cells.

“A critical aspect of our work was to generate relatively homogenous and stable populations of cancer stem-like cells that could then be used for screening,” says Tamer Onder, a former graduate student in Weinberg’s lab and co-first author of the study. (Onder is now a postdoctoral research fellow at Children’s Hospital in Boston.) “We were able to achieve this by inducing the cancer cells into an epithelial-to-mesenchymal transition using novel reagents that we had developed in the lab.”

With an ample number of stem cells in hand, the Broad-Whitehead team undertook a large-scale analysis of thousands of chemical compounds, applying automated methods to search for ones with activity against breast cancer stem cells. From a pool of more than 30 promising candidates, the researchers identified a compound with surprising potency.

The compound, called salinomycin, kills not only laboratory-created cancer stem cells, but also naturally occurring ones. Compared to a common chemotherapeutic drug prescribed for breast cancer (known as paclitaxel), salinomycin reduced the number of cancer stem cells by more than 100-fold. It also diminished breast tumor growth in mice.

To further dissect the function of salinomycin, the researchers also examined its genetic effects. Previous studies of tumors from breast cancer patients have revealed groups of genes that are highly active in cancer stem cells. Many of these same genes are linked with particularly aggressive tumors and poor patient prognoses. The researchers’ studies show that salinomycin (but not paclitaxel) treatment can decrease the activity of these genes, revealing a possible molecular basis for the chemical’s biological effects.

“Our work reveals the biological effects of targeting cancer stem cells,” says co-first author Piyush Gupta, a researcher at the Broad Institute. “Moreover, it suggests a general approach to finding novel anti-cancer therapies that can be applied to any solid tumor maintained by cancer stem cells.”

Although the new findings signal a noteworthy scientific milestone, it is still too early to know whether cancer patients will reap benefits from it. Additional research is needed to determine exactly how salinomycin works to kill cancer stem cells and if it can wield the same tumor-reducing power in humans as it does in mice. These types of analyses generally take several years to complete.

But even with such tempered enthusiasm, there is also cause for optimism. In the current study, just 16,000 chemical compounds were tested, of which a small subset showed toxicity against cancer stem cells. Therefore, deeper investigations of these compounds as well additional tests of broader collections of chemicals may yield other potential additions to the anti-cancer arsenal.

Paper cited:
Gupta et al. “Identification of selective inhibitors of cancer stem cells by high-throughput screening.” Cell, published online August 13, 2009

A complete list of the study’s authors and their affiliations:

Piyush B. Gupta,1,3,7,* Tamer T. Onder,1,2,7 Guozhi Jiang,1,3 Kai Tao,4 Charlotte Kuperwasser,4 Robert A. Weinberg,1,2,6,8,* and Eric S. Lander 1,2,3,5,8,*

1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

2Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA

3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

4Department of Anatomy and Cell Biology, Tufts University School of Medicine and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA

5Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA

6MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139

7These authors contributed equally to this work

8These authors contributed equally to this work

*Corresponding authors

About the Whitehead Institute for Biomedical Research
Whitehead Institute for Biomedical Research is a nonprofit, independent research and educational institution. Wholly independent in its governance, finances and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments. For additional information about Whitehead Institute, please visit www.whitehead.mit.edu.

About the Broad Institute of MIT and Harvard
The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of creative scientists to transform medicine with new genome-based knowledge. The Broad Institute seeks to define all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to www.broad.mit.edu

Information hot off the press


Take Care,

Jimmy B

CryoStim™ Cancer Treatment to Begin FDA Clinical Trials September 1, 2009,,Melanoma,, Jim Breitfeller

CryoStim™ Cancer Treatment to Begin FDA Clinical Trials September 1, 2009

Date:8/14/2009[“CryoStim™ represents a completely novel approach for therapeutic cancer design,” says Michael Har-Noy PhD, CEO and Chief Technical Officer. “Current therapies are not capable of eliminating every last cancer cell in the body and thus tumor recurrence is a common problem. If our experimental therapy is successful it would be possible to not only eliminate every last tumor cells, but also for the immune system to remember the tumor in order to prevent recurrence.”

Details about this cancer vaccine trial can be found at www.immunocare.net and at clinicaltrials.gov: NCT00861107. View complete details on products, trial and scientific literature at the company website.

About Immunovative:
Immunovative Therapies, Ltd. (ITL) is an Israeli-based biopharmaceutical company with US facilities in Carlsbad, California. Founded in May 2004 with financial support from Israel’s Office of the Chief Scientist, ITL is a graduate of the Misgav Venture Accelerator, a member of the world renowned Israel technological incubator program. The company was the Misgav Venture Accelerator’s candidate for the prize for the outstanding incubator project of 2006, awarded by the Office of the Chief Scientist. ITL specializes in the development of novel immunotherapy drug products that incorporate bioengineered living immune cells as the active ingredients for treatment of cancer, autoimmune and infectious disease.

Contact:
Michael Berger MD at 760-444-9040

In the Pacific Northwest contact Alan F. Hall JD at 425-774-9566



Dr. Flavell,
After 2 ½ years of stabilization from my first response to Melanoma, it appears that I may have relapsed. I will know once I have a full PET scan. My question is, why didn't my memory cells kick in? Could you help shed some light on this subject matter?

Need a copy of your paper "CD8 and T Cell Memory"

RESPONSE:

Did you receive immunotherapy ( anti-CTLA4 or PD-1 )? There are Tregs which suppress the memory responses which you may have; were immune responses measured?.The data on these Antibodies are sounding good . Contact Mario Sznol(Yale) who is a melanoma physician; I am a Ph.D so of little help on the specifics. Which paper are you referring to; we will send it.
Good Luck with all RAF

It may all come down to "BLAME IT ON THE TREGS"

So is my body making to many Tregs during activation which is shutting down the immune response? How do we block them into a normal ammount?

We need to get our hands around the Tregs.



Take Care,

Jimmy B

Genetic Profiling Of Tumors Could Have 'Immediate Impact' On Treating Cancer..Melanoma Jim Breitfeller

Genetic Profiling Of Tumors Could Have 'Immediate Impact' On Treating Cancer
Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 08 Aug 2009 - 0:00 PDT

New work by MIT cancer biologists shows that the interplay between two key genes that are often defective in tumors determines how cancer cells respond to chemotherapy.

The findings should have an immediate impact on cancer treatment, say Michael Hemann and Michael Yaffe, the two MIT biology professors who led the study. The work could help doctors predict what types of chemotherapy will be effective in a particular tumor, which would help tailor treatments to each patient.

"This isn't something that's going to take five years to do," says Yaffe, who, along with Hemann is a member of the David H. Koch Institute for Integrative Cancer Research at MIT. "You could begin doing this tomorrow."

The work could also guide the development of new chemotherapy drugs targeted to tumors with specific genetic mutations.

Hemann, Yaffe, and their colleagues report their results in the Aug. 15 issue of the journal Genes and Development. Koch Institute postdoctoral associates Hai Jiang and H. Christian Reinhardt are lead authors of the study, which the researchers say is one of the first examples of how genetic profiling of tumors can translate to improvements in patient treatment.

"There's a huge amount of genetic information available, but it hasn't made its way into clinical practice yet," says Hemann.

Genetic mystery

The research team focused on two proteins often involved in cancer, p53 and ATM. One of the first tumor suppressor genes discovered, p53 serves a watchdog function over a cell's genome, activating repair systems when DNA is damaged and initiating cell death if the damage is irreparable.

ATM is also involved in controlling the cell's response to DNA damage and is known to help regulate p53.

Mutations in p53, ATM or both are often seen in tumor cells. (ATM mutations occur in about 15 percent of cancers, and p53 is mutated in about 30 percent.)

Scientists have long tried to pin down a relationship between mutations in these genes and the effectiveness of DNA-damaging chemotherapy agents, but published studies have produced conflicting reports.

"It's been unclear whether the loss of p53 made tumors easier to treat or harder to treat. You could find examples of either case in the clinical literature," says Yaffe, adding that the same holds true for ATM.

The new study, conducted with human cancer cells, shows that tumors in which both p53 and ATM are defective are highly susceptible to chemotherapy agents that damage DNA. The double mutation prevents tumor cells from being able to repair DNA, and the cells commit suicide.

However, in cells where p53 is mutated but ATM is not, that type of chemotherapy is less effective. Remarkably, tumors where ATM is mutated but p53 is not turn out to be highly resistant to those types of chemotherapy.

With this new information, doctors could choose chemotherapy treatments based on the status of the p53 and ATM genes in a patient's tumor. Traditional DNA-damaging chemotherapy would be a good option for patients with both p53 and ATM mutations, but not for those with normal p53 and mutated ATM.

For patients who have normal ATM and mutated p53, other options might be better: New drugs that inhibit ATM, now in clinical trials, could improve tumors' susceptibility to chemotherapy in those patients.

The study shows the importance of studying cancer genes as a network, rather than trying to predict outcomes based on the status of single genes such as p53, says Robert Abraham, director of the cancer drug discovery program at Wyeth Pharmaceuticals.

Once ATM inhibitors are approved, "understanding the combined status of ATM and p53 should allow physicians to identify patients who should be treated with ATM inhibitors and chemotherapy and those for whom such a therapy could potentially be harmful," Abraham says.

In patients with normal p53 and mutated ATM, doctors could use drugs that target alternative DNA repair pathways. In their Genes and Development paper, the MIT researchers showed that treating such tumors with a drug that targets DNA-PK, another protein involved in DNA repair, renders them vulnerable to chemotherapy.

The MIT researchers collaborated with scientists from the Centre for Genotoxic Stress Research in Denmark, Helsinki University Central Hospital in Finland, and Uppsala University Hospital in Sweden.

The research was funded by the National Institutes of Health, the David H. Koch Fund, the Deutsche Forschungsgemeinschaft, the Deutsche Nierenstiftung, the Danish Cancer Society, the European Community, the Czech Ministry of Education and the Helsinki University Central Hospital Research Fund.

Source:
Jen Hirsch
Massachusetts Institute of Technology

Where did I hear about Genomic Profiling? It was right here on carepages.

Take Care,

Jimmy B

FDA Issues Final Rules to Help Patients Gain Access to Investigational Drugs..Melanoma..Jim Breitfeller

FDA NEWS RELEASE
For Immediate Release: Aug. 12, 2009

Media Inquiries: Karen Riley, 301-796-4674, karen.riley@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Issues Final Rules to Help Patients Gain Access to Investigational Drugs

The U.S. Food and Drug Administration published two rules today that seek to clarify the methods available to seriously ill patients interested in gaining access to investigational drugs and biologics when they are not eligible to participate in a clinical trial and don’t have other satisfactory treatment options.

To support the effort to help these patients, the agency also is launching a new Web site where patients and their health care professionals can learn about options for investigational drugs. In general, these options include being treated with a drug that has been approved by FDA, being given an investigational drug as part of a clinical trial, or obtaining access to an investigational drug outside of a clinical trial.

The new rule, “Expanded Access to Investigational Drugs for Treatment Use,” makes investigational drugs more widely available to patients by clarifying procedures and standards. The other rule, “Charging for Investigational Drugs Under an Investigational New Drug Application,” clarifies the specific circumstances and the types of costs for which a manufacturer can charge patients for an investigational drug when used as part of a clinical trial or when used outside the scope of a clinical trial.

“With these initiatives, patients will have the information they need to help them decide whether to seek investigational products,” said Margaret A. Hamburg, M.D., Commissioner of Food and Drugs. “For patients seeking expanded access to investigational drugs and biologics, the new rules make the process easier to understand.”

Clinical trials are studies of drugs and biologics that are still in development and have not yet been approved by the FDA. Many patients enroll in clinical trials to gain access to investigational therapies and contribute to finding out how well an investigational therapy works, and how safe it is for patients. Obtaining a drug or biologic under an expanded access program may be an option for some patients who are not able to enroll in clinical trials.

The FDA has allowed expanded access to experimental drugs and biologics since the 1970s. That access has allowed tens of thousands of patients with HIV/AIDS, cancer, and other conditions to receive promising therapies when no approved alternative is available.

“The final rules balance access to promising new therapies against the need to protect patient safety and seek to ensure that expanded access does not discourage participation in clinical trials or otherwise interfere with the drug development process,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Clinical trials are the most important part of the drug development process in determining whether new drugs are safe and effective, and how to best use them.”

Additional Information

Web site that explains the options for investigational drugs


Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs


Expanded Access to Investigational Drugs for Treatment Use (PDF - 603KB)


Charging for Investigational Drugs (PDF - 394KB)





Take Care,

Jimmy B