Preclinical data indicates that MDX-010 may be able to induce a reversible
state of autoimmunity, with an apparent correlation between the development of
drug-related autoimmunity and durable clinical responses. For this reason, a number of triasl in “immune” susceptilbe tumors, like melanoma ahve todate been conducted. nOnce technical challenges ahve been overcome, a number of trials were designed and carreid out. Immunization with a gp100-derived peptide modified to enhance its binding to major histocompatibility complex (MHC) HLA-A2 dramatically increased levels of peptide-specific CD8+ T cells in the peripheral blood. Importantly, these T cells recognized and killed a variety of melanoma cells that expressed the gp100 melanoma antigen and the restriction element HLA-A *0201 after culture in vitro. Administration of interleukin 2 (IL-2) following peptide immunization resulted in significantly more-objective tumor regressions than observed after IL-2 treatment alone15. However, many of these responses are partial and transient. Findings of some immune resposne led to the trial with high dose IL2 in melanoma.
GP100 when given with IL2 represents a combination treatment designed to work together. As such, the entire treatment is investigational.
Jared Gollob, Lawrence Flaherty, John Smith, Marc Ernstoff, Joe Clark, Kim Margolin, Yelena Novik, Jeff Sosman A Cytokine Working Group (CWG) Phase II Trial of a Modified gp100 Melanoma Peptide (gp100 (209M)) and High Dose Interleukin-2 (HD IL-2) Adminstered q3 Weeks in Patients with Stage Proc Am Soc Clin Oncol 20: 2001 (abstr 1423)
Willem W. Overwijk and Nicholas P. Restifo Creating Therapeutic Cancer Vaccines: Notes from the Battlefield Trends Immunol. 2001 January; 22(1): 5–7.