Rafat Solaiman

Tumor immunotherapy involves enhancing the ability of the immune system to specifically attack and kill cancer cells. One method of immunotherapy is adoptive cell transfer therapy (ACT), where tumor-specific CD8+ T cells isolated from a cancer patient are activated under defined conditions in the laboratory to produce a large number of CD8+ T cells, named cytotoxic T lymphocytes (CTLs), before being injected back into the patient. The efficacy of CD8+ T cells in ACT is likely thought to be strongly dependent on the activation methods used to expand the cells. We have previously investigated an established three-signal activation system that consists of an antigen signal, a second “costimulatory” signal and the soluble inflammatory cytokine IL-12. Previous studies show that CTLs derived from naive CD8+ T cells have greater antitumor activity than CTLs derived from memory CD8+ T cells. These CTLs were generated using an activation protocol lacking the IL-12 third signal that we now know to be critical to optimal CTL generation. We aimed to investigate functional differences between naive-derived CTLs and memory-derived CTLs when utilizing IL-12 in the activation regimen to control cancer upon transfer into a tumor-bearing host. Wild-type C57BL/6 mice were subcutaneously injected with B16 melanoma cells expressing ovalbumin (B16.OVA) and tumor growth was monitored over time following three different ACT injection groups: naive-derived CTLs, memory-derived CTLs, and no injection. Our findings suggest that naive-derived CTLs control tumor progression similarly or better than memory-derived CTLs but further trials must be completed to control cell counts.