Jump starting your Immune system with CTLA-4 & Interlukin-2 Therapy for Melanoma ---James Breitfeller

11/06/08 ---This is my Theory
Posted Nov 6, 2008 9:59am on Carepages

This is my Theory

The Interlukin-2IL-2, which works by stimulating killer T-cells to attack melanoma. In some cases with the right body chemistry, helps communicate that message to the killer T-cells and the body begins to fight off the Beast.
In other cases, your body chemistry is different than mine and may lack some sort protein/? or what ever. So in this case, the communication is lost like a drop signal from your cell phone. What you need is another Cell Tower to transmit that signal. That is where CTLA-4 coming in to play. It builds the tower to help with the communication. I may be over simplifying the biochemistry but I am not in the lab to do the right experiments. So, I have to take an educated guess.
As you can see, Dr. Kirkwood and I wanted to induce tumor regression by using my own immune system. If we could get my immune system to recognize the tumors as foreign, then we might have a fighting chance. So we decide to try the CTLA-4 Therapy,
Antitumor response with prolonged time to progression has been seen in patients with melanoma who have received either of the CTLA-4 antibodies and durable antitumor responses have been observed with ipilimumab in patients with melanoma ovarian cancer, prostate cancer, and renal cell carcinoma It has been seen, antitumor responses may be characterized by short-term progression followed by delayed regression.

An important, possibly unique, clinical characteristic of anti-CTLA-4 antibodies is that the duration of clinical response -- and even stable disease -- is often quite prolonged.

This is what I believe is going on in my case but I have no proof.

So lets combine the two clinical trials and that was done by Dr. Rosenberg at the National Cancer Institute.

So I took it apon myself to to a little research and this is what I came up with. I believe it all makes sense. I still may be over simplifying the actual process but I am not a biochemist. So Here goes:

Dendritic cells (DCs) are immune cells and form part of the our immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as Antigen-Presenting Cells (APC).
The dendritic cells are constantly in communication with other cells in the body. This communication can take the form of direct cell-to-cell contact based on the interaction of cell-surface proteins. An example of this includes the interaction of the receptor B7 of the dendritic cell with CD28 present on the lymphocyte. However, the cell-cell interaction can also take place at a distance via cytokines. These components of the immune system communicate with one another by exchanging chemical messengers. These proteins are secreted by cells and act on other cells to coordinate an appropriate immune response.
Cytokines include a diverse assortment of interleukins, interferons, and growth factors.One cytokine, interleukin 2 (IL-2), triggers the immune system to produce T cells. IL-2’s immunity-boosting properties have traditionally made it a promising treatment for several illnesses which include Hepatitis C and Melanoma.
There are several steps to activation of the immune system against a foreign molecule. The T cell receptor must first interact with the MHC molecule. The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is, in general, responsible for recognizing antigens bound to Major Histocompatibility Complex (MHC) molecules. MHC the most gene-dense region of the Human genome and plays an important role in the immune system, autoimmunity.

This first interaction involves the CD4 or CD8 proteins which form a complex with the CD3 protein to bind to the MHC molecule of the (APC). Antigen-presenting cell This is also called "Signal 1" and its main purpose is T cell activation.

However, this is insufficient for producing a T cell response by itself. In fact, lack of further stimulatory signals sends the T cell into anergy. Anergy is a term in immunobiology that describes a lack of reaction by the body's defense mechanisms to foreign substances.

The Second costimulatory signal necessary to continue the immune response can come from B7-CD28 and CD40-CD40L interactions. The primary role of the B7 proteins is to give a second signal to the T cell. The B7 protein/receptor is present on the Antigen-presenting cell and is able to interact with the CD28 receptor on the T cell surface; this is also known as "Signal 2". There are other activation signals which play a role in immune responses.
On these T cells there is are family receptors whose job is downregulate the T cell activation so the immune system maintains metabolic equilibrium so the immune system doesn’t start an autoimmune response and cause it to attack itself. One of these receptors is Cytotoxic T lymphocyte-associated antigen (CTLA4).

It was hypothesized back in the 1980’s that if you replaced the CTLA4 with Anti-CTLA4 that it might block the B7 receptor causing an enhancement of the T-cell activation, leading to a more robust antitumor immune response.

It was shown in mice with a disrupted CTLA-4 genes that their immune response ran unabated causing autoimmunity which was fatal.

It was also shown that the anti-CTLA-4 antibodies had a greater affinity to CTLA-4 than the B7 receptor. So by doing the CTLA-4 Therapy, it allowed signal 1 to become active.

So in the presents of the CTLA-4 antibody Therapy, I my case, we may have extended the antitumor response of the T-cells. This left Signal 1 active.

We then, hit the immune system with High dose of IL-2. This must have stimulated the cell to cell communication (Signal 2) causing the immune response to kick in against the foreign molecule (The Tumor)

AS YOU GUESSED IT, I MUST HAVE JUMP STARTED MY IMMUNE SYSTEM!!!!!!

Just don't know how long it will last.

Jimmy B