Trial watch: dendritic cell vaccination for cancer immunotherapy

Abstract

Dendritic- cells (DCs) have received considerable attention as potential targets for the development of anticancer vaccines. DC-based anticancer vaccination relies on patient-derived DCs pulsed with a source of tumor-associated antigens (TAAs) in the context of standardized maturation-cocktails, followed by their reinfusion. Extensive evidence has confirmed that DC-based vaccines can generate TAA-specific, cytotoxic T cells. Nonetheless, clinical efficacy of DC-based vaccines remains suboptimal, reflecting the widespread immunosuppression within tumors. Thus, clinical interest is being refocused on DC-based vaccines as combinatorial partners for T cell-targeting immunotherapies. Here, we summarize the most recent preclinical/clinical development of anticancer DC vaccination and discuss future perspectives for DC-based vaccines in immuno-oncology.

Keywords: Antigen cross-presentation; DAMPs; TLR signaling; clinical trial; immune checkpoint blockers; plasmacytoid dendritic cells; tumor-infiltrating lymphocytes.

Figure 1.

Overview of current strategies of dendritic cell vaccination for cancer therapy. ACPP, acid phosphatase, prostate; AML, acute myeloid leukemia; CEA, carcinoembryonic antigen; CLL, chronic lymphocytic leukemia; CRC, colorectal cancer; DC, dendritic cell; DKK1, dickkopf WNT signaling pathway inhibitor 1; EPS8, epidermal growth factor receptor pathway substrate 8; HCC, hepatocellular carcinoma; KRAS, KRAS proto-oncogene, GTPase; MUC1, mucin 1, cell surface associated; NSCLC, non-small cell lung cancer; NY-ESO-1 (official name: CTAG1B), cancer/testis antigen 1B; CMV pp65, cytomegalovirus 65 kDa phosphoprotein; PSA (official name: KLK3), kallikrein related peptidase 3; RCC, renal cell carcinoma; RNF43, ring finger protein 43; TAA, tumor-associated antigen; TERT, telomerase reverse transcriptase; WT1, WT1 transcription factor.