Cancer vaccines are the next frontier in immunotherapy

While traditional vaccines are dedicated to the prevention of a wide range of infectious diseases, cancer vaccines, which have received much attention in recent years, aim to focus the power of the body's immune system on the elimination of tumor cells. Although existing immunotherapies (e.g., immune checkpoint inhibitors and chimeric antigen receptor T cells) have achieved significant results in the field of tumor therapy, cancer vaccines have unique advantages, such as the ability to target intracellular antigens other than tumor-specific surface antigens, and may even trigger new tumor-specific T cell responses.

Types of cancer vaccines

Tumor antigens are frequently classified as tumor-specific antigens (TSA), which include viral antigens and neoepitopes resulting from nonsynonymous cell mutations, and tumor-associated antigens (TAA), which comprise tissue-specific antigens and developmental-specific antigens. Cancer vaccines work by transporting tumor antigens through APC and presenting them to CD8+ T lymphocytes with HLA-I. Cancer vaccines can stimulate immune responses against tumor antigens by activating DCs carrying tumor antigens. Different cancer vaccines employ different strategies for co-localizing tumor antigens with cross-presented DCs.

Predefined antigens

Prior to therapy, predefined antigens are more precisely characterized. The frequency of expression of predefined antigens across patient cohorts can be used to further classify them. Shared antigens are antigens expressed in a large enough proportion of patients that immunologists may target cancer patients using conventional assays, and the resultant shared antigen vaccines can target both TSA and TAA. Personalized antigens are specific to the immunized individual, are often composed of TSA neoepitopes, and are less prevalent in large groups of patients.

Vaccines against predefined personalized antigens

Personalized antigens, as opposed to shared antigens, target only one patient, most typically the neoepitope TSA. The advantage of targeting customized antigens is that it achieves better specificity and can be used with immune checkpoint inhibitor treatment to boost T-cell responsiveness in patients who respond to therapy. The use of next-generation sequencing makes the development of personalized antigenic vaccinations more possible and successful.

Isolated or in situ anonymous antigens

Anonymous antigens are not defined prior to treatment and their further classification can be done by loading position with the APC, rather than by antigen identity.

Isolated anonymous antigenic vaccine, APC co-localization

Isolated anonymous antigenic vaccines are derived from excised tumor cells (excisional biopsies) that are lysed and processed into a more antigenic form and co-localized with APCs. The injected tumor cells may be absorbed and delivered to the autologous APC, or the tumor cells themselves may present their antigen to the T cells.

In situ anonymous antigenic vaccine, APC co-localization

In situ anonymous antigen vaccines are similar to in vitro vaccines in that they function by inducing APC recruitment and tumor antigen loading and activation so that APCs can effectively cross-trigger tumor-reactive T cells.

Many failures have occurred in cancer vaccine research, and the present success of products like as CAR-T and bispecific T-cell conjugates has verified the practicality of cancer vaccine concepts to some extent. However, how to enhance cCD1 cross-presentation and how to detect cross-triggered tumor-reactive T cells in vaccinated individuals are unanswered concerns.

Measuring efficacy before assessing antitumor efficacy is the gold standard for cancer treatment development. Studies have shown that the antitumor T-cell response is critical to the antitumor efficacy of vaccines. Enzyme-linked immunosorbent spot (ELISPOT) or flow cytometry analyses are available to assess the function of tumor-reactive T cells using T cell-peptide co-cultures of predefined antigen vaccines. In response to the current new therapeutic approach of combining vaccines with checkpoint blockade, investigators have also developed assays such as mutation-associated neoantigen functional expansion of specific T cell (MANAFEST) assay that combine functional T cell reactivity assays (for neoepitopes) with practical descriptive assays (e.g. TC sequencing) that allow sequential testing of the latter in blood or tumor to measure antitumor T-cell responses. Such assays go beyond neoepitope reactivity and probe the reactivity of whole tumor cells to allow measurement of immune responses to anonymous tumor antigen vaccines.

A fan of biotechnology who likes to post articles in relevant fields regularly