Vaccine immunotherapy for prostate cancer: from mice to men.
Preclinical studies demonstrated the ability of an adenovirus/PSA (Ad/PSA) vaccine to induce strong anti-PSA immune responses, and these responses were capable of destroying prostate-specific antigen (PSA)-secreting mouse prostate tumors. A series of preclinical studies have demonstrated the superiority of the Ad/PSA vaccine to other PSA vaccines for the induction of anti-PSA immune responses, the ability of Ad/PSA vaccination combined with cytokine gene therapy and the TLR9 agonist CpG to enhance the anti-prostate tumor immunotherapy, and the reduction of negative regulatory elements when the vaccine was combined with 5-fluoruracil administration. A phase I clinical trial of the Ad/PSA vaccine in men with metastatic castrate-resistant prostate cancer demonstrated the safety of the vaccine even at the highest single dose permitted by the FDA. Currently, a phase II trial of the Ad/PSA vaccine is underway treating patients in two protocols. Thus far 81 patients have been enrolled and vaccinated. Early results from the patients evaluated to date demonstrated the induction of anti-PSA T cell responses, and the majority of patients evaluated at this time had demonstrated an increase in PSA doubling times.
Department of Urology, University of Iowa, 375 Newton Road, Iowa City, IA, 52242, USA, david-lubaroff@uiowa.edu.
David M
DM
Lubaroff
Daniel
D
Vaena
James A
JA
Brown
Pamela
P
Zehr
Karen C
KC
Griffith
Erica
E
Brown
Julie
J
Eastman
Kenneth
K
Nepple
Ambika
A
Kattula
Richard D
RD
Williams
D000256:Adenoviridae; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007610:Kallikreins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051217:Toll-Like Receptor 9 / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen