Results of PROSPECT: A randomized phase 3 trial of PROSTVAC-V/F (PRO) in men with asymptomatic or minimally symptomatic metastatic, castration-resistant prostate cancer.

Gulley, James L.; Borre, Michael; Vogelzang, Nicholas J.; Ng, Siobhan; Agarwal, Neeraj; Parker, Chris; Pook, David; Rathenborg, Per; Flaig, Thomas W.; Carles, Joan; Shore, Neal D.; Chen, Liddy; Heery, Christopher R.; Gerritsen, Winald R.; Priou, Frank

doi:10.1200/jco.2018.36.15_suppl.5006

Cited by 10 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phase III trial was conducted after a phase II trial showed that PROSTVAC-V/F increased overall survival by 8.5 months (Kantoff et al 2010). Unfortunately, this large randomized phase III study, which enrolled 1297 patients across 15 countries, failed to confirm the increase in overall survival, with a hazard ratio for overall survival of 1.02 (Gulley et al 2018). Several other vaccine constructs are in various states of testing for prostate cancer.…”

Section: Combining Anti-pd-1/pd-l1 With Vaccinesmentioning

confidence: 99%

Immunotherapy for Prostate Cancer

Venturini

Drake

2018

Cold Spring Harb Perspect Med

View full text Add to dashboard Cite

Immunotherapy with agents that block immune checkpoints is a mainstay of therapy for several common tumor types; so far, prostate cancer is not among those treated using this method. The observed lack of activity in prostate cancer is not due to a lack of testing; several agents have been evaluated both alone and in combination. Although several combination strategies show some promise, it appears likely that a greater understanding of the prostate cancer tumor microenvironment and baseline immune response will be required to optimize future treatment strategies.

show abstract

Section: Combining Anti-pd-1/pd-l1 With Vaccinesmentioning

confidence: 99%

Immunotherapy for Prostate Cancer

Venturini

Drake

2018

Cold Spring Harb Perspect Med

View full text Add to dashboard Cite

show abstract

“…Despite negative results of some phase III trials and limited licensure (47), there is great hope that cancer vaccines can become more successful. Microbial proteins in pathogen-associated malignancies may have an advantage over native tumor antigens due to reduced self-tolerance.…”

Section: Discussionmentioning

confidence: 99%

Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8+ T Cells within Polyomavirus-Driven Merkel Cell Carcinomas

Jing

Ott

Church

et al. 2020

Cancer Immunology Research

View full text Add to dashboard Cite

Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to TAg specific T cells. Strategies to increase CD8 þ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigenpresenting cell (aAPC) system and confirmed TAg recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8 þ T cells recognizing 1-8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8 þ TIL epitopes and prior TIL data indicated that 97% of patients with MCPyV þ MCC had HLA alleles with the genetic potential that restrict CD8 þ T-cell responses to MCPyV TAg. The LT AA 70-110 region was epitope rich, whereas the oncogenic domains of TAg were not commonly recognized. Specific recognition of TAg expressing DCs was documented. Recovery of MCPyV oncoprotein-specific CD8 þ TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicates that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of TAg can be modified without impacting immunogenicity.

show abstract

“…In addition, it incorporates three co-stimulatory molecules for immune activation and has been used in several trials in various malignancies. In men with CRPC, the PROSTVAC vaccine phase 3 trial, using PSA as antigen, failed to positively influence OS [146], although phase 2 trials were encouraging [147,148]. An analysis of immune response to the PROSTVAC vaccine on pooled data from several clinical trials conducted similarly reported that 68% of the tested patients exhibited evidence of cross-priming with immune responses mounted against TAAs not found in the vaccine, for example, MUC-1, PSMA, PAP and PSCA, a phenomenon known as antigen spreading [149].…”

Section: Viral Vectorsmentioning

confidence: 99%

Cancer Vaccines

Henriquez¹,

Arkenau²,

Dutoit³

et al. 2019

Cancer Immunotherapy and Biological Cancer Treatments

View full text Add to dashboard Cite

Recent advances in immuno-oncology have allowed for the design of more specific and efficient cancer vaccine approaches. There has been an improvement in molecular biology techniques, as well as a greater understanding of the mechanisms involved in the activation and regulation of T cells and the interplay between the components of the immune system and the escape mechanisms used by cancer cells and the tumour microenvironment. As a result, many interesting developments in therapeutic cancer vaccines are ongoing, with influence on survival still to be proven. The spectrum of tumour antigens that are recognised by T cells is still largely unchartered and, most importantly, dynamically evolving over time, driven by clonal evolution and treatment-driven selection. Vaccine approaches currently in development and tested in clinical studies are based on tumour antigens specifically identified for each tumour type, on tumour cells or dendritic cells, the latter having the potential to be modified to incorporate immunostimulatory genes. However, interplay between the immune system and the tumour and the inhibitory mechanisms developed by tumour cells to subvert immune responses are crucial issues that will need to be targeted in order for efficient therapeutic vaccines to emerge.

show abstract

Results of PROSPECT: A randomized phase 3 trial of PROSTVAC-V/F (PRO) in men with asymptomatic or minimally symptomatic metastatic, castration-resistant prostate cancer.

Cited by 10 publications

References 0 publications

Immunotherapy for Prostate Cancer

Immunotherapy for Prostate Cancer

Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8+ T Cells within Polyomavirus-Driven Merkel Cell Carcinomas

Cancer Vaccines

Contact Info

Product

Resources

About