Vaccination with tumor cell lysate plus CpG oligodeoxynucleotides elicits tumor-specific T cells with potent antitumor efficacy in adoptive immunotherapy (131.31)

Abstract

Abstract This study investigated whether tumor-specific T cells can be elicited by vaccination with tumor cell lysate plus CpG oligodeoxynucleotides (CpG/lysate) for adoptive immunotherapy. Vaccination of C57BL/6 mice with syngeneic EL-4 tumor cell lysate mixed with a CpG-B ODN (CpG 685) significantly increased the number of T cells and activated DCs in the draining lymph nodes (DLN). Mice vaccinated with CpG/lysate developed protective immunity against EL-4 tumor challenge with a significant longer median survival time (P<0.01). The CpG/lysate-primed DLN T cells were expanded in a 5-day culture with anti-CD3 mAb and IL-2, and adoptively transferred into EL-4 tumor-bearing mice following cyclophosphamide (CY) treatment. Therapy with CY plus CpG/lysate-primed T cells induced an 80% tumor-free survival rate whereas EL-4 mice in the control groups all died within 30 days. When the mice cured by CpG/lysate-primed T cells were re-challenged with EL-4 tumor 2 months later, all the mice (100%) survived without tumor growth, suggesting the persistence of T cell-mediated antitumor immunity. The efficacy of CpG/lysate-primed T cells was comparable to DC/lysate vaccine-primed T cells in adoptive immunotherapy. Cell-depletion studies showed that CD4 T cells play a pivotal role in CpG/lysate vaccine-induced antitumor effects. The results suggest that CpG/lysate vaccine provides an effective approach to induce host antitumor immunity and tumor-reactive T cells for adaptive immunotherapy.