Analysis of therapeutic vaccine platforms in advanced prostate cancer: mechanisms and clinical context.
| Vaccine name | Trial phase | NCT number | Biomarkers/Target | Description | Sponsor | Mechanistic insight & developmental context |
|---|---|---|---|---|---|---|
| Sipuleucel-T | Phase III (led to FDA approval) | NCT00065442 | PAP | A dendritic cell vaccine that primes the immune system to target prostate cancer cells expressing PAP. | Dendreon Pharmaceuticals | First-in-class cellular immunotherapy. Demonstrates that activating the immune system against a single, non-mutated self-antigen (PAP) can yield a survival benefit, though its modest effect size highlights the challenge of breaking immune tolerance. |
| RhoC anticancer vaccine | Phase I/II | NCT03199872 | RhoC (Rho family GTPase) | RhoC-targeted vaccine to stimulate T-cell immunity against cancer. | RhoVac APS | Targets RhoC, a protein involved in cancer metastasis. Represents a strategy to prevent recurrence by targeting a driver of progression, moving beyond targets like PSA/PAP. |
| PROSTVAC-V/F + GM-CSF | Phase III | NCT01322490 | PSA | A poxvirus-based vaccine designed to activate an immune response against prostate cancer cells. | Bavarian Nordic | Despite strong immunogenicity and positive early-phase results, this well-designed poxviral vaccine failed in Phase III, underscoring the difficulty of achieving clinical efficacy with vaccine monotherapy in advanced, immunosuppressive mCRPC. |
| PAP plus GM-CSF | Phase II | NCT01341652 | PAP | Peptide vaccine with GM-CSF for immune boost. | University of Wisconsin, Madison | Highlights the importance of patient selection; efficacy may be confined to a specific, more immunologically responsive disease state (e.g., rapid PSA-DT indicating higher disease burden/antigen exposure). |
| DC vaccine with tumor mRNA | Phase I/II | NCT01197625 | Tumor-associated antigens | A personalized dendritic cell vaccine using mRNA from individual tumors to enhance immune response. | Oslo University Hospital | A highly personalized approach that bypasses the need for predefined tumor antigens. It leverages the full spectrum of a patient’s tumor mutations to generate a polyclonal T-cell response, though manufacturing complexity is a barrier. |
| Prodencel | Phase I | NCT05533203 | Tumor-associated antigens | A therapeutic vaccine using dendritic cells to prime the immune system against prostate. | Shanghai Humantech Biotechnology Co. Ltd | Represents the continued development of the autologous dendritic cell platform pioneered by sipuleucel-T, exploring its application with potentially different antigen-loading or maturation protocols. |
| GVAX® prostate cancer vaccine | Phase III | NCT01436968 | PSMA | Vaccine based on oncolytic viruses combined with radiation therapy to target prostate cancer cells. | Candela Therapeutics, Inc. | Combines in situ vaccination (oncolytic virus lysing cells and releasing antigens) with standard radiotherapy. The goal is to convert the tumor into an immunogenic hub, a strategy distinct from pre-manufactured vaccines. |
| TENDU vaccine | Phase I | NCT04701021 | Tumor-specific neoantigens | A personalized DNA neoantigen vaccine for patients post-prostatectomy (status: Completed). | Ultimovacs ASA | A neoantigen-targeting DNA vaccine. This represents the cutting edge of vaccine technology, aiming to elicit responses against truly tumor-specific mutations (neoantigens) to avoid tolerance and maximize safety. |
NCT: National Clinical Trial; DC: dendritic cell; GM-CSF: granulocyte-macrophage colony-stimulating factor; mCRPC: metastatic castration-resistant prostate cancer; PAP: prostatic acid phosphatase; PSA: prostate-specific antigen; PSMA: prostate-specific membrane antigen; PSA-DT: PSA doubling time. Adapted from https://clinicaltrials.gov/ and Meng et al. [6] (CC-BY).