Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

作者：Lotem Michal^*; Machlenkin Arthur; Hamburger Tamar; Nissan Aviram; Kadouri Luna; Frankenburg Shoshana; Gimmon Zvi; Elias Orit; Ben David Inna; Kuznetz Anna; Shiloni Eitan; Peretz Tamar

来源：Clinical Cancer Research, 2009, 15(15): 4968-4977.

DOI：10.1158/1078-0432.CCR-08-3320

Purpose: Autologous melanoma cells display a broad variety of tumor antigens and were used for treatment of American Joint Committee on Cancer stages III and IV melanoma as an adjuvant or active therapy. Survival data and immune response were evaluated in vaccinated patients.
Experimental Design: Forty-seven patients received 2,4-dinitrophenyl-conjugated autologous melanoma vaccine as an adjuvant (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood sampled before vaccination and after five or eight vaccine doses was evaluated against melanoma cells and autologous peripheral blood mononuclear cells using IFN gamma enzyme-linked immunospot. Serum levels of antilivin, an inhibitor of apoptosis, and anti-gp100 IgG were determined.
Results: The immunologic effect of the vaccine differed between the two groups of patients. In the adjuvant group, there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035) after vaccination and an increase in antimelanoma CD4 T cells correlating with improved overall survival (P = 0.04). In the therapeutic group, there was no objective tumor regression; antimelanoma T-cell reactivity increased by a small amount, stayed the same, or in some cases decreased. In all patients, a significant increase was noted in CD4 T-cell reactivity against autologous peripheral blood mononuclear cells (P = 0.02), which did not affect survival. Increased antilivin IgG was associated with improved survival. Expression of MHC class II on melanoma cells was vital for the immunogenicity of the vaccine.
Conclusion: Autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival. Patients with active metastatic disease generally displayed reduced immune response and gained little from active immunization.

• 出版日期2009-8-1