Dendritic Cell-Based Vaccine Efficacy: Aiming for Hot Spots

Abstract

Many approaches for cancer immunotherapy have targeted dendritic cells (DCs), directly or indirectly, for the induction of antitumor immune responses. DC-based vaccines have been developed using a wide variety of ex vivo DC culture conditions, antigen (Ag) source and loading strategies, maturation agents, and routes of vaccination. Adjuvants are used to activate innate immune cells at the vaccine injection site, to promote Ag transport to the draining lymph nodes (LNs) and to model adaptive immune responses. Despite years of effort, the effective induction of strong and durable antitumor T-cell responses in vaccinated patients remains a challenge. The study of vaccine interactions with other immune cells in the LNs and, more recently, in the injection site has opened new doors for understanding antitumor effector T-cell licensing and function. In this review, we will briefly discuss the relevant sites and up-to-date facts regarding possible targets for antitumor vaccine refinement. We will focus on the processes taking place at the injection site, adjuvant combinations and their role in DC-based vaccines, LN homing, and modeling vaccine-induced immune responses capable of controlling tumor growth and generating immune memory.

Antigen-Presenting Cell/Tumour Cell Hybrid Vaccines in Cancer Immunotherapy

“…In a clinical study, the intradermal injection of DC-tumour hybrid vaccine resulted in superior antitumour response compared to other routes [77]. Other pre-clinical data suggest that the provision of a third signal with the hybrid vaccines may generate a better response rate [78,79]. Finally, the use of DC/tumour fusion vaccines may demonstrate significant efficacy when combined with other treatment modalities.…”

Current immunotherapeutic strategies in hepatocellular carcinoma: recent advances and future directions

“…40 Additional measures for DC vaccines have been adopted to overcome the immunosuppressive effects of tumors, including use of mature DCs by ex vivo activation and adding strong stimuli for activation. 41 Until now, DC vaccines have been tested in patients with HCC in several studies with different designs, such as ex vivo-matured DCs pulsed with tumor lysate in patients with advanced HCC and adjuvant DC vaccines following microwave ablation or TACE. [42][43][44] Most recently, a phase I/IIA study using a multiple TAA (AFP, GPC-3, and MAGE-1)-pulsed adjuvant DC vaccine after primary treatment (surgery, ablation, or TACE) showed safety and extension of time to progression (TTP) in the vaccination group.…”

Dendritic Cell Based Vaccine for Human Tuberculosis

“…The surface marker for both mature and immature is basically the same but with marked quantitative differences, Table 2 ,DCs are hetero-genus group of cells that displayed difference in various anatomic sites ,cell surface phenotypes and functions. Thus ,its sub-grouped into three subsets, Table 3 .DCs expressed a sort of cell plasticity [23,24,25].…”

“…These vaccines composed of microbial antigens are often made with adjuvant , Table 4 , that activate DCs .There are urgent need for both preventive and therapeutic vaccine for tuberculosis replacing the currently blamed as ineffective the BCG [ 31].Since till now no approved dendritic cell based tuberculosis vaccine are developed, evaluated and licensed. However several experimental DCs based tuberculosis vaccine tested iv-vitro, ex-vivo and in-vivo to the rank of laboratory animal evaluations are being documented all over the world [23,30,31,32]. …”

“…iii-Blood samples with an anti-coagulant collected from the patients, dendritic cells are separated, purified and cultured in cell culture system in presence of antigen source, loading agent ,maturation agent [23] .…”