A phase I study of sequential vaccinations with recombinant Fowlpox-PSA (L155)-TRICOM (rF)alone, or in combination with recombinant vaccinia-PSA (L155)-TRICOM (rV), and the role of GM-CSF, in patients (Pts) with prostate cancer
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.90140.2522
ISSN1527-7755
AutoresPhilip M. Arlen, James L. Gulley, William Dahut, Lisa Skarupa, Steven Morin, Mary Pazdur, N R Todd, Dennis Panicali, K. Y. Tsang, Jeffrey Schlom,
Tópico(s)Hepatitis B Virus Studies
Resumo2522 Background: Vaccine strategies targeting PSA represent a novel approach in the treatment of prostate cancer. Since PSA is a “self” antigen, vaccine strategies utilizing this as a target must be developed to enhance its immunogenicity. Previous studies have shown that the induction of T-cell responses directed against a self-antigen is associated with anti-tumor activity but not toxicity. Two novel vaccines have been developed: (a) a recombinant vaccinia virus containing the entire PSA transgene with a modified agonist epitope and three costimulatory molecule transgenes rV and (b) a similar recombinant fowlpox virus rF. Methods: This Phase I study evaluated the safety of a diversified prime/boost vaccine strategy: priming with rV and monthly boosts using rF. All pts had progressive metastatic prostate cancer. This trial also examined the combination of these agents with recombinant GM-CSF (rG) as well as two doses of fowlpox-GM-CSF (rF-G). The first of 5 cohorts utilized a fixed dose of rF alone, the second cohort tested the safety of a priming vaccination with rV followed by monthly rF boosting. Cohorts 3,4, and 5 provided safety data combining cohort 2 with rG or two doses of rF-G respectively. Results: Accrual (n=15) has been achieved. Thirteen pts remain on study. No dose limiting toxicities have been observed. Pt characteristics: median age = 64 years (range 48–80), median PSA = 191.7 ng/ml (range 2.6–2943), median Gleason score = 8 (range 7–9). Seven of 9 evaluable pts treated for at least 3 months have not demonstrated progression on CT or bone scan and remain on study. One pt in cohort 2 has a PSA decline of >35%. Immunologic studies are ongoing to measure changes in PSA specific T cells. Conclusions: Based on the safety data from this clinical trial, we have initiated the randomized Phase II component of this study to compare the immunologic effects of the above vaccine strategy alone, with r-G, or with either of 2 doses of rF-G. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics
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