Effect of Blocking of CTLA-4 Immune Checkpoint on the Growth of Two Murine tumors Displaying Different Immunogenicity

ARIEL STRAZZA; RAÚL RUGGIERO; DANIELA MONTAGNA; GRACIELA DRAN; PAULA CHIARELLA

Mar del Plata

Congreso; LXI Reunión Científica Anual de la SociedadArgentina de Investigación Clínica (SAIC) y LXIV de la Sociedad Argentina de Inmunología; 2016

SAI-SAIC

CTLA-4 is an immune checkpoint expressed in T-reg and activated T cells thattransmits inhibitory signals to T cells and down-regulates immune responses. On this basis, there is a growing interest in the possible therapeutic benefits of blocking CTLA-4 as a means of enhancing immune responses against cancer. In fact ipilimumab ? a monoclonal anti-CTLA- 4 antibody ? was recently approved for the treatment of human advanced melanoma. However, despite these promissory expectations, most experimental studies in this topic were performed in mice bearing strongly immunogenic chemically-induced tumors that are not the best models for clinical cancer. Herein, we have studied the effect of an antibody against CTLA-4 on the growth of two murine tumors displaying widely different degrees of immunogenicity: the strongly immunogenic methylcholanthrene-induced MC-C fibrosarcoma and the spontaneous LMM3 carcinoma displaying undetectable immunogenicity. Tumor-bearing mice (n = 6 mice per group) received 3 doses of 100 μg i.p. of anti-CTLA- 4 antibody each 4 days starting at day 3, 10 or 17 after the s.c. inoculum with 5x105 MC-C or LMM3 tumor cells, that is when the tumor was incipient (I), medium (M) or large (L). Results were expressed as tumor volume (mm 3 ) [media ± SE] at day 35 of tumor growth. MC-C: Control Group (without treatment): 2,027± 63; Treated Groups: I: 314 ± 74 (p