Abstract
Purpose: 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. Experimental Design: 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 rV 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. Conclusion: This vaccine regimen can be safety given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3353-3362 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 11 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. / Gulley, James L.; Arlen, Philip M.; Bastian, Anne; Morin, Steven; Marte, Jennifer; Beetham, Patricia; Tsang, Kwong Yok; Yokokawa, Junko; Hodge, James W.; Ménard, Cynthia; Camphausen, Kevin; Coleman, C. Norman; Sullivan, Francis; Steinberg, Seth M.; Schlom, Jeffrey; Dahut, William.
In: Clinical Cancer Research, Vol. 11, No. 9, 01.05.2005, p. 3353-3362.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer
AU - Gulley, James L.
AU - Arlen, Philip M.
AU - Bastian, Anne
AU - Morin, Steven
AU - Marte, Jennifer
AU - Beetham, Patricia
AU - Tsang, Kwong Yok
AU - Yokokawa, Junko
AU - Hodge, James W.
AU - Ménard, Cynthia
AU - Camphausen, Kevin
AU - Coleman, C. Norman
AU - Sullivan, Francis
AU - Steinberg, Seth M.
AU - Schlom, Jeffrey
AU - Dahut, William
PY - 2005/5/1
Y1 - 2005/5/1
N2 - Purpose: 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. Experimental Design: 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 rV 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. Conclusion: This vaccine regimen can be safety given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.
AB - Purpose: 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. Experimental Design: 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 rV 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. Conclusion: This vaccine regimen can be safety given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.
UR - http://www.scopus.com/inward/record.url?scp=20944441967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20944441967&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-04-2062
DO - 10.1158/1078-0432.CCR-04-2062
M3 - Article
C2 - 15867235
AN - SCOPUS:20944441967
VL - 11
SP - 3353
EP - 3362
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -