Combining chemotherapy and autologous peptide‐pulsed dendritic cells provides survival benefit in stage IV melanoma patients

Abstract

Background and Objectives: We examined retrospectively whether the combination of standard dacarbazine (DTIC) and/or fotemustine chemotherapy and autologous peptide-loaded dendritic cell (DC) vaccination may improve survival of stage IV melanoma patients. Furthermore, a small cohort of long-term survivors was studied in more detail. Patients and methods: Between 1998 and 2008, 41 patients were vaccinated at least three times with DCs while receiving chemotherapy and compared to all other 168 patients in our database who only received chemotherapy (1993-2008). Results: Median life expectancy of patients receiving additional DC-vaccination was 18 months, compared to eleven months for patients under standard chemotherapy alone. In contrast to patients with other haplotypes, the HLA-A1/A1 subset of DC-treated patients showed significantly lower median survival (12 vs. 25 months). Autoantibodies were frequently detected in serum of both vaccinated and non-vaccinated patients, and there was no correlation between titers, loss or appearance of autoantibodies and survival. Additionally, phenotyping of DCs and PBMCs also did not reveal any conspicuous correlation with survival. Conclusions: Combining standard chemotherapy and DC vaccination appears superior to chemotherapy alone. The impact of HLA haplotypes on survival emphasizes the importance of a careful selection of patients with specific, well-defined HLA haplotypes for future vaccination trials using peptide-pulsed DCs, possibly combined with checkpoint inhibitors.

Dendritic Cell-Derived Exosomes in Cancer Immunotherapy

“…Prospects for this immunotherapy aim at developing high-immunogenicity DEXs with genetic modifications to achieve a larger scale of cell-free immunotherapy. Furthermore, the use of immune adjuvants and their combination with other cancer therapeutic modalities may enable DEXs to stimulate T cells more effectively in the future [ 71 , 103 , 106 , 109 ]. In conclusion, DEX-based antitumor vaccines are still in the preliminary stage of exploration.…”

Recent Advances and Challenges in Cancer Immunotherapy

“…DC vaccines have shown promising results in clinical trials as monotherapy, including resulting in improved OS. Additional adjuvants, such as chemotherapy, could improve vaccine efficacy by inducing the release of danger signals by tumor cells and enhancing the immune response [ 113 , 114 , 115 , 116 ].…”

Recent Advances and Future Perspective of DC-Based Therapy in NSCLC

“…It is important to define the optimal dose of chemotherapy or radiotherapy for combination treatment with immunotherapy, as high doses of chemo- and radiotherapy can induce cell death of immune cells as well ( 37 ). The synergistic effect of chemotherapy to DC vaccination was recently validated in a human melanoma study ( 44 ). For NSCLC, this synergistic effect of both chemotherapy and radiotherapy with DC vaccination was confirmed in mouse models ( 45 – 47 ).…”