A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies

Abstract

Anticancer vaccines have been extensively studied in animal models and in clinical trials. While vaccination can lead to tumor protection in numerous murine models, objective tumor regressions after anticancer vaccination in clinical trials have been rare. B16 is a poorly immunogenic murine melanoma that has been extensively used in anticancer vaccination experiments. Because B16 has been widely used, different vaccination strategies can be compared. We reviewed the results obtained when B16 was treated with five common vaccine types: recombinant viral vaccines, DNA vaccines, dendritic cell vaccines, whole-tumor vaccines, and peptide vaccines. We also reviewed the results obtained when B16 was treated with vaccines combined with adoptive transfer of tumor antigen-specific T cells. We found several characteristics of vaccination regimens that were associated with antitumor efficacy. Many vaccines that incorporated xenogeneic antigens exhibited more potent anticancer activity than vaccines that were identical except that they incorporated the syngeneic version of the same antigen. Interleukin-2 enhanced the antitumor efficacy of several vaccines. Finally, several effective regimens generated large numbers of tumor antigen-specific CD8(+) T cells. Identification of vaccine characteristics that are associated with antitumor efficacy may aid in the development of more effective anticancer vaccination strategies.

Vaccination‐induced functional competence of circulating human tumor‐specific CD8 T‐cells

“…Cells (10 6 ) were incubated with tetramers (1 lg ml À1 , 60 min, 4 C) and then with antibodies (30 min, 4 C). For intracellular assessment of cytokines, 10 6 MiniMACS purified CD8 pos T-cells were first prestained with PE-labeled tetramers for 30 min at 4 C. Without this prestaining, the visualization of antigen-specific T-cells would be inefficient due to TCR downregulation (Supporting Information Fig. 1), precluding comprehensive quantification of functional cells among antigen-specific T-cell populations.…”

“…Functional avidity appears to be essential, as well as the capacity of T-cells to recognize naturally processed and presented tumor antigens. 10 Moreover, the precursor frequency of naïve T-cells plays a key role. 11 Finally, it is important that T-cells are competent for proliferation, cell survival, homing, effector functions and generation of immunological memory.…”

Vaccines for the treatment of non-small cell lung cancer: Investigational approaches and clinical experience

“…Vaccines can also be produced by loading dendritic cells with tumor antigens [15], which may prime both CD8+ T cell and antibody responses, but again dendritic cell vaccines are difficult to manufacture and standardize [11]. Whilst peptide vaccines are easy to produce and modify, they may have poor immunogenicity unless efficient delivery systems and/or immunoadjuvants are used [15,24,31]. The use of peptides also restricts the immune response to a particular T cell repertoire and narrows the target population to patients expressing the appropriate MHC molecules [31].…”

“…Recombinant protein-based vaccines can induce both CD8+ and CD4+ T cell responses against multiple epitopes and there is no need for MHC selection of patients [31]. Viral vaccines can generate CD8+ T cell and antibody responses; however, the effectiveness of viral vaccines may be limited by the generation of neutralizing immune responses against viral proteins [24]. Alternative non-viral approaches to antigen delivery, including liposomal-based vaccines which strongly enhance the uptake of antigens by APCs, are showing promise [32,33].…”

“…Each approach has advantages and disadvantages [24]. It should be noted that antigens tend to be poorly immunogenic by themselves and that vaccines generally require the inclusion of potent immunoadjuvants to induce robust antitumor immune responses [25].…”