Dendritic-Tumor Fusion Cell-Based Cancer Vaccines

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4+ and CD8+ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving clinical outcomes by DC-tumor FC-based cancer vaccines.

How cells fuse

“…For instance, prostate cancer cells fuse with stromal and skeletal muscle cells, and breast cancer cells fuse with normal mammary gland cells and with endothelial cells (Kerbel et al, 1983). Hybrid cells generated by cancer cell/dendritic cell fusion can actually induce an anti-tumor immune response and can potentially be used as a treatment for colorectal and renal cancer (Koido, 2016). However, in most cases, such hybrid cells have cancer stem cell properties with elevated metastatic potential, proliferation rate, and drug resistance (reviewed in Bastida-Ruiz et al, 2016; Noubissi and Ogle, 2016; Gast et al, 2018; Wang et al, 2018).…”

Immunotherapy for Gastric Cancer: Time for a Personalized Approach?

“…An alternative approach to target multiple antigens is the fusion of DCs with whole tumor gastric cells to generate DC-tumor hybrids, e.g., by the electrofusion technique. These hybrid cells have the advantage of combining the potent antigen presenting capacity of DCs with the availability of the full repertoire of antigens expressed by tumor cells [ 127 , 128 ]. To circumvent the disadvantage of the limited availability of viable autologous tumor cells for the fusion, allogeneic GC cells may be used instead of autologous GC cells (cross-priming antigens) Therefore, it is not necessary to match the HLA haplotype between patients and allogeneic tumor cells used to generate the fusion.…”

Immunotherapy Based on Dendritic Cells in Bladder Cancer Treatment

“…Научная основа этого подхода состоит в том, что аллогенные линии опухолевых клеток могут экспрессировать те же основные ОАА, что и клетки аутологичной опухоли. Хорошо охарактеризованные аллогенные линии опухолевых клеток, имеющие высокую пролиферативную активность in vitro, способны экспрессировать достаточное количество ОАА для нагрузки и активации ДК, кроме того, их возможно стандартизировать и использовать в крупномасштабном производстве вакцин [31].…”