A comprehensive review highlights the progress, challenges, and future prospects of prostate cancer vaccines, emphasizing their potential to deliver long-lasting immune responses despite hurdles in clinical application.
Study: Vaccine Therapies for Prostate Cancer: Current Status and Future Outlook. Image Credit: Jarun Ontakrai/Shutterstock.com
Recently, scientists reviewed available literature to explore advancements in prostate cancer (PCa) vaccines. Their findings were published in Vaccines.
Prostate cancer and treatments
Prostate cancer (PCa) is a common malignancy affecting the male genitourinary system. Standard treatments, such as androgen deprivation therapy (ADT), often prove ineffective for patients with castration-resistant prostate cancer (CRPC) or metastatic disease (mCRPC).
Although second-generation anti-androgen therapy, radiotherapy, and chemotherapy offer some benefits, they do not provide a complete cure.
Tumor immunotherapy, which uses the body’s immune system to target and eliminate cancer cells, has emerged as a promising avenue. Among the primary approaches are adoptive cell therapy, immune checkpoint inhibitors (ICIs), and cancer vaccines.
Cancer vaccines introduce tumor antigens that activate T-cells, which then target and destroy cancer cells. However, challenges such as tumor heterogeneity complicate the development of universal vaccines.
Prostate cancer vaccines
Prostate cancer vaccines include several types, such as dendritic cell vaccines, viral vaccines, DNA/mRNA vaccines, and peptide vaccines.
The effectiveness of these immunotherapies can be influenced by biological factors such as age and hormone levels, as well as the immunosuppressive tumor microenvironment, which may allow tumors to evade immune responses.
Dendritic cell vaccines
The first FDA-approved PCa vaccine, Sipuleucel-T (PROVENGE), uses ex vivo activation of peripheral blood dendritic cells with a fusion protein of granulocyte-macrophage colony-stimulating factor (GM-CSF) and prostate acid phosphatase (PAP).
PROVENGE activates CD4+ and CD8+ T-cells, inducing an immune response against tumors. Clinical trials have demonstrated reduced prostate-specific antigen (PSA) levels and improved outcomes, especially with early treatment or in combination with radiotherapy.
Cellular vaccines
The GVAX/PCa vaccine, a genetically modified cancer cell vaccine, utilizes LNCaP and PC-3 cell lines to produce GM-CSF. Clinical trials have shown its potential in reducing PSA levels in recurrent PCa patients and in improving outcomes for mCRPC.
While promising, findings like the complete remission of PCa with GVAX, cyclophosphamide, and degarelix require further validation.
Peptide vaccines
Peptide vaccines target tumor antigens to elicit immune responses. Phase III trials have shown these vaccines can effectively lower PSA levels and treat CRPC and mCRPC.
Additionally, combining peptide vaccines with low-dose cyclophosphamide has demonstrated enhanced efficacy in reducing PSA levels.
Nucleic acid vaccines
DNA and mRNA vaccines introduce genetic sequences encoding tumor antigens to activate immune responses. DNA vaccines work by producing tumor antigens in antigen-presenting cells (APCs), which activate T-cells.
mRNA vaccines offer advantages such as higher expression efficiency, lower risk of mutations, and a favorable safety profile. Both approaches show potential for eliciting targeted immune responses.
Viral vaccines
Viral vaccines use modified viruses, such as adenoviruses, to deliver tumor antigens to host cells. The recombinant plasmid vaccine PROSTVAC, containing a PSA transgene, represents a notable example in this category.
These vaccines aim to generate robust immune responses capable of targeting and eliminating tumor cells.
Conclusion
While prostate cancer vaccines hold promise, challenges remain, including the complexity of tumor microenvironments and the need for further validation of current findings.
Continued research is essential to improve the effectiveness and accessibility of these therapies, offering hope for more targeted and durable treatment options in the future.
