Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer.

摘要

Novel strategies for the therapy of recurrent ovarian cancer are warranted. Wereport a study of a combinatorial approach encompassing dendritic cell (DC)-basedautologous whole tumor vaccination and anti-angiogenesis therapy, followed by theadoptive transfer of autologous vaccine-primed CD3/CD28-co-stimulatedlymphocytes. Recurrent ovarian cancer patients for whom tumor lysate wasavailable from prior cytoreductive surgery underwent conditioning withintravenous bevacizumab and oral metronomic cyclophosphamide, sequentiallyfollowed by bevacizumab plus vaccination with DCs pulsed with autologoustumor cell lysate supernatants, lymphodepletion and transfer of 5 × 10(9)autologous vaccine-primed T-cells in combination with the vaccine. Feasibility,safety as well as immunological and clinical efficacy were evaluated. Sixsubjects received this vaccination. Therapy was feasible, well tolerated, andelicited antitumor immune responses in four subjects, who also experiencedclinical benefits. Of these, three patients with residual measurable diseasereceived outpatient lymphodepletion and adoptive T-cell transfer, which was well tolerated and resulted in a durable reduction of circulating regulatory T cellsand increased CD8(+) lymphocyte counts. The vaccine-induced restoration ofantitumor immunity was achieved in two subjects, who also demonstrated clinicalbenefits, including one complete response. Our findings indicate thatcombinatorial cellular immunotherapy for the treatment of recurrent ovariancancer is well tolerated and warrants further investigation. Severalmodifications of this approach can be envisioned to optimize immunological andclinical outcomes.