Here Goes!!! I am going to Spill the Beans!!!!!! Melanoma Jim Breitfeller

"The induction of an immunological antitumor response capable of eradicating metastatic tumors is the ultimate goal of immunotherapy. We have recently shown that this can be achieved by interleukin 2 (IL-2) therapy directed to the tumor microenvironment by a recombinant antibody–IL-2 fusion protein. It is not known, however, whether this curative treatment is associated with a predominance of T cells carrying specific T cell receptor variable ? regions (TCRBV) or the presence of clonally expanded T cells."

Activation of preexisting T cell clones by targeted interleukin 2 therapy

Per thor Straten,* Per Guldberg,* Tina Seremet,* Ralph A. Reisfeld,†‡ Jesper Zeuthen,* and Jürgen C. Becker§
*Department of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark; †Department of Immunology, Scripps Research Institute, La Jolla, CA 92037; and §Department of Dermatology, School of Medicine, D-97080 Würzburg, Germany
‡To whom reprint requests should be addressed at: Department of Immunology, Scripps Research Institute, IMM 13, R218, 10550 North Torrey Pines Road, La Jolla, CA 92037.
Communicated by Frank J. Dixon, Scripps Research Institute, La Jolla, CA
Received February 19, 1998; Accepted April 30, 1998.

"Melanoma is a highly malignant tumor but several lines of evidence suggest that it is capable of eliciting a specific immune response, i.e., a number of melanoma-associated antigens have been identified and the presence of clonotypic T cells has been demonstrated in melanoma lesions (1–4). Therefore, several immunomodulatory therapeutic approaches were initiated to improve the prognosis of melanoma patients. Interleukin 2 (IL-2) is one of the most potent antitumor cytokines known quote (5), and was recently approved for treatment of metastatic melanoma. However, objective responses induced by systemic IL-2 therapy are still insufficient, and the associated side effects are severe (6). These findings are due to the fact that a systemic application of IL-2 disregards the paracrine nature of this cytokine under physiological conditions (7).

As a means to target IL-2 directly to the tumor site, we have recently shown that human IL-2 can be genetically engineered as a fusion protein with the chimeric mouse–human mAb 14.18 which recognizes the ganglioside GD2, retaining both antigen binding and cytokine activity (8).

Furthermore, we have shown that treatment with this antibody–IL-2 fusion protein can eradicate human hepatic and pulmonary melanoma metastases in severe combined immunodeficient mice (9) as well as autologous murine B16 melanomas (10). Although it was shown in these studies that tumor eradication was dependent on CD8+ T cells, it is not known whether tumor clearance is associated with a clonal expansion of T cells. Furthermore, it remains to be established whether such a clonal expansion would be due to a de novo induction or to the activation and expansion of preexisting T cell clones. Here, we demonstrate both the overexpression of certain T cell receptor variable β regions (TCRBV) as well as the clonal expansion of T cells in melanoma lesions subsequent to targeted IL-2 therapy.

However, clonally expanded T cells were also detectable prior to the
thrapy, suggesting that antibody–IL-2-targeted therapy acts as an activator rather than an inducer of an antitumor T cell response."

Source:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21154
Activation of preexisting T cell clones by targeted interleukin 2 therapy


"Melanoma and the Magic Bullet (Monoclonal Antibodies)"

You have read it here First!!!!!!!!!

I still have write the IL-2 part, But I believe the concept is all there.

Now I have to work on the protocol of the "Antibody-IL-2 therapy"

That is why my therapy "Antibody-IL-2 therapy" worked!!!!!!!!

I can smell the sweet Success!!!!!!!



Jimmy B