PURPOSE: We have previously reported on the safety and immunologic response of a poxvirus-based vaccine encoding prostate-specific antigen (PSA) used in combination with radiation therapy in patients with localized prostate cancer. We hypothesized that a "metronomic" dose of interleukin 2 (IL-2) as a biological adjuvant would cause less toxicity while maintaining immunologic response. EXPERIMENTAL DESIGN: Eighteen patients with localized prostate cancer were treated in a single-arm trial using previously established doses of vaccine and radiation therapy. The vaccine used was a recombinant vaccinia virus engineered to encode PSA admixed with a recombinant vaccinia encoding the costimulatory molecule B7.1, followed by booster vaccinations with a recombinant fowlpox vector expressing PSA. Patients received a total of eight planned vaccination cycles, once every 4 weeks, with granulocyte-macrophage colony-stimulating factor given on days 1 to 4 and interleukin 2 (IL-2) at a dose of 0.6 MIU/M2 given from days 8 to 21 after each vaccination. Definitive external beam radiation therapy was initiated after the third vaccination cycle. Patients were evaluated for safety and immunologic response. Toxicity and immunologic activity were compared with the previously reported regimen containing a higher dose of IL-2. RESULTS: Seventeen of 18 patients received all eight cycles of vaccine with IL-2. Five of eight HLA-A2+ patients evaluated had an increase in PSA-specific T cells of > or =3-fold. Toxicities were generally mild, with only seven vaccination cycles of 140 given resulting in grade 3 toxicities possibly attributable to IL-2. CONCLUSIONS: Metronomic-dose IL-2 in combination with vaccine and radiation therapy is safe, can induce prostate-specific immune responses, and has immunologic activity similar to low-dose IL-2, with markedly reduced toxicities.
PURPOSE: We have previously reported on the safety and immunologic response of a poxvirus-based vaccine encoding prostate-specific antigen (PSA) used in combination with radiation therapy in patients with localized prostate cancer. We hypothesized that a "metronomic" dose of interleukin 2 (IL-2) as a biological adjuvant would cause less toxicity while maintaining immunologic response. EXPERIMENTAL DESIGN: Eighteen patients with localized prostate cancer were treated in a single-arm trial using previously established doses of vaccine and radiation therapy. The vaccine used was a recombinant vaccinia virus engineered to encode PSA admixed with a recombinant vaccinia encoding the costimulatory molecule B7.1, followed by booster vaccinations with a recombinant fowlpox vector expressing PSA. Patients received a total of eight planned vaccination cycles, once every 4 weeks, with granulocyte-macrophage colony-stimulating factor given on days 1 to 4 and interleukin 2 (IL-2) at a dose of 0.6 MIU/M2 given from days 8 to 21 after each vaccination. Definitive external beam radiation therapy was initiated after the third vaccination cycle. Patients were evaluated for safety and immunologic response. Toxicity and immunologic activity were compared with the previously reported regimen containing a higher dose of IL-2. RESULTS: Seventeen of 18 patients received all eight cycles of vaccine with IL-2. Five of eight HLA-A2+ patients evaluated had an increase in PSA-specific T cells of > or =3-fold. Toxicities were generally mild, with only seven vaccination cycles of 140 given resulting in grade 3 toxicities possibly attributable to IL-2. CONCLUSIONS: Metronomic-dose IL-2 in combination with vaccine and radiation therapy is safe, can induce prostate-specific immune responses, and has immunologic activity similar to low-dose IL-2, with markedly reduced toxicities.
Authors: Miljenko V Pilepich; Kathryn Winter; Colleen A Lawton; Robert E Krisch; Harvey B Wolkov; Benjamin Movsas; Eugen B Hug; Sucha O Asbell; David Grignon Journal: Int J Radiat Oncol Biol Phys Date: 2005-04-01 Impact factor: 7.038
Authors: Chie Kudo-Saito; Jeffrey Schlom; Kevin Camphausen; C Norman Coleman; James W Hodge Journal: Clin Cancer Res Date: 2005-06-15 Impact factor: 12.531
Authors: James L Gulley; Philip M Arlen; Anne Bastian; Steven Morin; Jennifer Marte; Patricia Beetham; Kwong-Yok Tsang; Junko Yokokawa; James W Hodge; Cynthia Ménard; Kevin Camphausen; C Norman Coleman; Francis Sullivan; Seth M Steinberg; Jeffrey Schlom; William Dahut Journal: Clin Cancer Res Date: 2005-05-01 Impact factor: 12.531
Authors: M Bolla; D Gonzalez; P Warde; J B Dubois; R O Mirimanoff; G Storme; J Bernier; A Kuten; C Sternberg; T Gil; L Collette; M Pierart Journal: N Engl J Med Date: 1997-07-31 Impact factor: 91.245
Authors: V P Khatri; T A Fehniger; R A Baiocchi; F Yu; M H Shah; D S Schiller; M Gould; R T Gazzinelli; Z P Bernstein; M A Caligiuri Journal: J Clin Invest Date: 1998-03-15 Impact factor: 14.808
Authors: N J Meropol; G M Barresi; T A Fehniger; J Hitt; M Franklin; M A Caligiuri Journal: Cancer Immunol Immunother Date: 1998-08 Impact factor: 6.968
Authors: Claudia Palena; Romaine I Fernando; Mary T Litzinger; Duane H Hamilton; Bruce Huang; Jeffrey Schlom Journal: Exp Biol Med (Maywood) Date: 2011-03-22
Authors: Elizabeth A Tindall; Hoa N Hoang; Melissa C Southey; Dallas R English; John L Hopper; Graham G Giles; Gianluca Severi; Vanessa M Hayes Journal: BMC Cancer Date: 2010-02-25 Impact factor: 4.430
Authors: James L Gulley; Ravi A Madan; Kwong Y Tsang; Caroline Jochems; Jennifer L Marté; Benedetto Farsaci; Jo A Tucker; James W Hodge; David J Liewehr; Seth M Steinberg; Christopher R Heery; Jeffrey Schlom Journal: Cancer Immunol Res Date: 2013-11-04 Impact factor: 11.151