Vicky’s Treatment timeline:
1) Diagnosis 5/10/06
2) Excision and sentinel node biopsy 5/16/06. SN positive, MM 3.3 mm, amelanotic, ulcerated (I did just read that the ulcerated variant does seem to do well with high-dose interferon in terms of prolonging survival)
3) Elective radical lymph node dissection, right groin, 5/30/06 2 more positive lymph nodes
4) High-dose iv interferon all of July 2006, followed by subcutaneous interferon MWF for 2 months.
5) Enroll in anti-CTLA-4 study as adjuvant therapy for stage 3 MM with Dr. Jeffrey Weber at USC. First dose of intravenous infusion of anti-CTLA-4, dose of 10 mg/kg early Nov 2006, second dose was Jan. 9, 2007.
6) Chest CT, routine, for the study, was positive for bilateral pulmonary nodules on 1/18/07
7) Lung biopsy positive for MM on 2/03/07
8) First course of high-dose IL-2 was March 2007
9) 60% reduction in tumor burden on April 23 CT scans
10) Second course of IL-2 in June 2007 ( I believe I got 14 of 14 doses during the 3rd cycle or week 1 of the second course.
11) Complete response seen on CT 8/01/07
12) Took an elective 5th cycle of IL-2 in early September of 2007- got quite sick and stopped. I think I got around 9 doses that last time.
I also did some rounds of IFN before Anti-CTLA-4 and HD interleukin -2. I had an added therapy and that was with DTIC + Patrin-2.
So I began to search on Interferon Therapy and came across a paper called “Interferon in Oncological Practice: Review of Interferon Biology, Clinical Applications, and Toxicities” by ERIC JONASCH, FRANK G. HALUSKA
Massachusetts General Hospital, Boston, Massachusetts, USA
It reviewed the biology of interferon. Once I read it, it dawned on me that Interferon alpha may have played the most important part of our treatment. It was the stage manager, who set the major histocompatibility complex molecules (MHC) in place. Without the upregulation of the correct MHC presented, the cytotoxic T cells (CTLs) would not know where the tumor target was. Higher MHC I expression increases presentation of tumor peptides to cytotoxic T cells, while the immunoproteasome processes tumor peptides for loading onto the MHC I molecule, thereby increasing the recognition and killing of infected cells by T cells. Interferon also activated the NK cells and macrophages. They inturned secreted IFN gamma which upragulated MHC II for the CD4 helper cells.
I postulate that IFN therapy prior to the Anti-CTLA-4 and HD IL-2 had synergistic effect on the overall treatment that Vicky Bucay and I had.
IFN alpha is one of the major cytokines responsible for upregulating
MHC class I protein expression and for inducing MHC class II proteins on
a variety of leukocytes and epithelial cells. IFN has also been shown to
be the major cytokine responsible for activating or otherwise regulating the action of mononuclear phagocytes.
Take Care,
Jimmy B
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