Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects

Abstract

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce long-term antitumor memory, causing tumor regression, eradicate minimal residual illness, and prevent non-specific or unpleasant effects. These vaccines can assist in the elimination of cancer cells from various organs or organ systems in the body, with minimal risk of tumor recurrence or metastasis. Vaccines and antigens for anticancer therapy are discussed in this review, including current vaccine adjuvants and mechanisms of action for various types of vaccines, such as DNA- or mRNA-based cancer vaccines. Potential applications of these vaccines focusing on their clinical use for better therapeutic efficacy are also discussed along with the latest research available in this field.

Keywords: antigen; cancer; immunotherapy; nucleic acid; peptides; vaccine.

Figure 1

Manipulation of antitumor immune responses by therapeutic vaccination. (a) Therapeutic vaccines are administered after the tumor is diagnosed, at the time of interactions between the tumor and the immune system that correspond to part (c). Therapeutic vaccines boost immunity against minimal residual disease and prevent the outgrowth of metastases shown in parts (b,c). A vaccine based on an autologous tumor was administered in an immunostimulatory preparation (with adjuvant) that can activate Langerhans cells—dendritic cells (DCs) that reside in the epidermis. Activated Langerhans cells take up the tumor antigens and traffic to the draining lymph node in which they present antigens to T-cells. B-cells are also activated, and the expected outcome is clonal expansion of tumor-specific T-cells and the production of tumor-specific antibodies. (b) Tumor-specific T-cells migrate to the sites of tumor metastases where they attempt to kill tumor cells that express antigens contained in the vaccine. (c) Metastases that continue to grow are composed of tumor cells that lack antigens recognized by T-cells and antibodies or are otherwise resistant to immune destruction.

Figure 2

Proposed mechanism of action of prophylactic vaccine. (a) Prophylactic vaccination is used to manipulate antitumor immune responses. Individuals who are at high risk of developing tumors or have been diagnosed with premalignant changes in target tissues would receive prophylactic vaccines prior to the occurrence of tumors. A vaccine based on antigens expected to be expressed by the anticipated tumor is administered in an immunostimulatory preparation (with adjuvant) that can activate Langerhans cells—epidermal dendritic cells (DCs). Activated Langerhans cells transport tumor antigens to the draining lymph node, where they present antigens to T-cells. B-cells are also activated, with the expected result of clonal expansion of tumor-specific T-cells and antibody production. This clonal expansion of effector cells is followed by the generation of a pool of memory cells specific for the tumor antigen/s over time. (b) If a tumor grows in the future, tumor antigens that reach the draining lymph node will reactivate tumor-specific memory cells and trigger a rapid secondary immune response. This response will be distinguished by a large number of effector T-cells, a high titer of antibodies, and continuous activation of DCs at the tumor site, allowing for continuous processing and presentation of tumor antigens and further immune amplification. (c) Since the incipient tumor has not grown large and heterogeneous, it is easily eliminated by the prepared immune response. Furthermore, the memory compartment is expanded by this tumor-mediated boost.

Figure 3

Mechanism of action of cancer vaccines (created with biorender.com).

Figure 4

Representation of activation of CD4⁺ and CD8⁺ epitopes through antigen presentation regulated by the innate immune system, which inhibits proliferation of tumor tissue (Created with biorender.com).

Figure 5

Diagrammatical representation of gene-based cancer vaccines (created with biorender.com).