CD4+ T cells are critical to the therapeutic efficacy of TAA-based cancer vaccines and control of recurrences (48.11)

Abstract

Abstract The role of CD4+ T cells remains ambiguous in cancer immunotherapy. We herein addressed this issue using a novel form of soluble 4-1BBL (SA-4-1BBL) costimulatory molecule as an effective adjuvant component of HPV E7 and survivin as TAA-based vaccines in E7 expressing TC-1 cervical and survivin over expressing 3LL lung cancer preclinical models, respectively. Vaccination of C57BL/6 mice on day 6 having established tumors with SA-4-1BBL admixed with E7 or survivin TAAs resulted in the eradication of TC-1 and 3LL tumors in 70% and 80% of mice, respectively, along with generation of tumor specific long-term memory that prevented tumor recurrence on second challenge. The in vivo depletion of CD4+ T cells one day before tumor challenge significantly compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) models. In marked contrast, the depletion of CD4+ T cells one day prior to vaccination did not significantly alter the therapeutic efficacy of the vaccines. However, these mice had compromised immunological memory since a second challenge of 3LL on day 60 resulted in tumor development in the majority (85.7%) of mice. Taken together, this study demonstrates an indispensable role of CD4+ T cells in priming immune responses against cancer as well as establishment of long-term memory.