Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine
| Title: | Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine |
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| Authors: | Ellen Wargowski, Laura E. Johnson, Jens C. Eickhoff, Lauren Delmastro, Mary Jane Staab, Glenn Liu, Douglas G. McNeel |
| Source: | Journal for ImmunoTherapy of Cancer, Vol 6, Iss 1, Pp 1-12 (2018) |
| Publisher Information: | BMJ Publishing Group, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | Sipuleucel-T, DNA vaccine, Prostate cancer, Prostatic acid phosphatase, Immune monitoring, Clinical trial, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Abstract Background Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC). Methods Eigthteen patients with mCRPC were randomized to receive sipuleucel-T alone or followed by intradermal immunization with pTVG-HP DNA vaccine. Patients were followed for time to progression, and immune monitoring was conducted at defined intervals. Results Overall, patients were followed for a median of 24 months. 11/18 patients completed treatments as per protocol. No treatment-associated events > grade 2 were observed. Th1-biased PAP-specific T-cell responses were detected in 11/18 individuals, and were not statistically different between study arms. Higher titer antibody responses to PAP were detectable in patients who received pTVG-HP booster immunizations. Median time to progression was less than 6 months and not statistically different between study arms. The median overall survival for all patients was 28 months. Conclusions These findings suggest that prime-boost vaccination can augment and diversify the type of immunity elicited with anti-tumor vaccination in terms of T-cell and humoral immunity. Future studies will explore DNA as priming immunization rather than a booster immunization. Trial registration NCT01706458. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2051-1426 |
| Relation: | http://link.springer.com/article/10.1186/s40425-018-0333-y; https://doaj.org/toc/2051-1426 |
| DOI: | 10.1186/s40425-018-0333-y |
| Access URL: | https://doaj.org/article/af87872586dd4df4a01fa1683e476315 |
| Accession Number: | edsdoj.f87872586dd4df4a01fa1683e476315 |
| Database: | Directory of Open Access Journals |
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