Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer.
OBJECTIVE
Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy.


METHODS
We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations.


RESULTS
Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated.


CONCLUSIONS
This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.
Gulley
James L
JL
Laboratory of Tumor Immunology and Biology, Medical Oncology Clinical Research Unit, Radiation Oncology Branch, and Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Arlen
Philip M
PM
Bastian
Anne
A
Morin
Steven
S
Marte
Jennifer
J
Beetham
Patricia
P
Tsang
Kwong-Yok
KY
Yokokawa
Junko
J
Hodge
James W
JW
Ménard
Cynthia
C
Camphausen
Kevin
K
Coleman
C Norman
CN
Sullivan
Francis
F
Steinberg
Seth M
SM
Schlom
Jeffrey
J
Dahut
William
W
D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D017430:Prostate-Specific Antigen