Immunotherapy Vaccines for Prostate Cancer Treatment

Abstract

Background: Therapeutic tumor vaccines have emerged as a compelling avenue for treating patients afflicted with advanced prostate cancer (PCa), particularly those experiencing biochemical relapse or ineligible for surgical intervention. This study serves to consolidate recent research findings on therapeutic vaccines targeting prostate tumors while delineating prevalent challenges within vaccine research and development.

Methods: We searched electronic databases, including PubMed, Web of Science, Embase, and Scopus, up to August 31, 2024, using keywords such as 'vaccine', 'prostate cancer', 'immunotherapy', and others. We reviewed studies on various therapeutic vaccines, including dendritic cell-based, antigen, nucleic acid, and tumor cell vaccines.

Results: Studies consistently showed that therapeutic vaccines, notably DC vaccines, had favorable safety profiles with few adverse effects. These vaccines, with varied antigenic formulations, demonstrated strong clinical outcomes, as indicated by metrics such as PSA response rates (9.5%-58%), extended PSA doubling times (52.9%-89.7%), overall survival durations (17.7-33.8 months), two-year mortality rates (0%-12.5%), biochemical relapse rates (42%-73%), and antigen-specific immune responses (33.3%-71.4% in responsive groups).

Conclusion: While clinical data for tumor vaccines have illuminated robust evidence of tumoricidal activity, the processes of their formulation and deployment are riddled with complexities. Combining vaccines with other therapies may enhance outcomes, and future research should focus on early interventions and deciphering the immune system's role in oncogenesis.

Keywords: immunotherapy; prognosis; prostate cancer; therapeutic tumor vaccine; tumor treatment.

FIGURE 1

Tumor infiltration of therapeutic vaccines. Diverse therapeutic vaccines containing tumor antigens undergo processing by APCs upon entry into the body. These antigens are subsequently loaded onto MHC class I or MHC class II molecules on the APCs' surface within the fluid circulation, facilitating their transportation to lymphatic organs. Within these organs, APCs are stimulated to secrete IL‐12 and IL‐15, activating native or memory CD8⁺ and CD4⁺ T lymphocytes. This activation occurs through interactions between the TCR and homologous receptor‐ligand pairs. Simultaneously, CD4⁺ T lymphocytes release TNF and IL‐12, augmenting the anti‐tumor functions of CD8⁺ T lymphocytes. Ultimately, the activated T lymphocytes are mobilized around tumor cells via chemokines and cytokines, including the CXCR and CCL families, to facilitate the elimination of tumor cells. APC, antigen‐presenting cells; CCL, C‐C motif chemokine ligand; CXCR, C‐X‐C motif chemokine receptor; MHC, major histocompatibility complex; TCR, T‐cell receptor; TNF, tumor necrosis factor.

FIGURE 2

Combination of immunotherapies in prostate cancer. Comprehensive immunotherapeutic approaches to eradicate prostate tumor cells encompass therapeutic vaccines formulated with tumor antigen proteins or peptides, along with viral vectors carrying antigen genes. In vivo, these antigen‐loaded vaccines stimulate APC functions, bolster DC activity, modulate CD4⁺ T cells to regulate T regulatory cell functions, and enhance the anti‐tumor capabilities of CD8⁺ T cells. Additionally, CAR‐T therapy and other immune adjuvant therapies can deploy tumor‐specific CD8⁺ T cells directly infused into the body to achieve anti‐tumor efficacy. Furthermore, immune checkpoint inhibitors possess the capacity to obstruct inhibitory pathways like PD‐1/PD‐L1 and CTLA‐4 in tumor microenvironments, countering the suppression of T‐cell functions and reinforcing anti‐tumor efficiency. Oncolytic viruses, engineered to selectively replicate and eliminate tumor cells, augment the immunotherapeutic methods' ability to efficiently present tumor antigens to the immune system. These viruses can function as stand‐alone therapies or in combination with other immunotherapeutic methods. The synergistic use of these methods facilitates the generation and activation of tumor‐specific T cells, culminating in a collaborative killing effect, offering a therapeutic strategy to counteract existing immunotherapy challenges. APC, antigen‐presenting cells; CAR‐T therapy, chimeric antigen receptor T‐cell immunotherapy; CTLA‐4, cytotoxic T‐lymphocyte‐associated protein 4; DC, dendritic cell; PD‐1/PD‐L1, programmed death 1/programmed death ligand 1.