A clinical study has been completed to evaluate safety and clinical outcomes of a vaccine containing multiple tumor antigens and costimulatory molecules in patients with metastatic carcinoma. Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary endpoint of this study was to evaluate safety, with immunologic and clinical responses as secondary endpoints of this novel vaccine regimen. Twenty-five patients were treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM, composed of B7.1, ICAM-1, and LFA-3) engineered into vaccinia (PANVAC-V) as a prime and fowlpox (PANVAC-F) as booster vaccinations. The vaccine was well-tolerated. Apart from injection-site reaction, no grade II or greater toxicity was seen in more than 2% of the cycles. Three of 8 patients tested developed a CD8-mediated CEA-specific immune response, and 6 of 9 patients developed a CD4-mediated CEA-specific immune response. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of > 20% in the size of large liver metastasis. This vaccine strategy appears to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this novel vaccine, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted for a range of human carcinomas. Other accomplishments are described in the following publications: Aragon-Ching B, Williams K, Gulley J. Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer. Front Biosci. 4957-71, 2007. [Journal] Gulley J, Madan R, Arlen P. Enhancing efficacy of therapeutic vaccinations by combination with other modalities. Vaccine. 2007. In Press. [Journal] Schlom J, Arlen P, Gulley J. Cancer vaccines: moving beyond current paradigms. Clin. Cancer Res. 3776-82, 2007. [Journal] Arlen P, Skarupa L, Pazdur M, Seetharam M, Tsang K, Grosenbach D, Feldman J, Poole D, Litzinger M, Steinberg S, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley J. Clinical safety of a viral vector-based prostate cancer vaccine strategy. J Urol. 2007. In Press. [Journal] Theoret M, Arlen P, Pazdur M, Dahut W, Schlom J, Gulley J. Phase I trial of an enhanced prostate-specific antigen-based vaccine with anti-CTLA-4 antibody in patients with metastatic androgen-independent prostate cancer. Clin Genitourinary Cancer. 5: 347-50, 2007. [Journal] Wu S, Dahut W, Gulley J. The use of bisphosphonates in cancer patients. Acta Oncologica. 581-91, 2007. [Journal] Madan R, Lieberman R, Gulley J, Dahut W, Arlen P. A significant PSA response to low dose ketoconazole in a patient with non-metastatic androgen independent prostate cancer (AIPC) and a review of the literature. Amer J Therapeutics. 14: 310-3, 2007. [Journal] Yokokawa J, Bera TK, Palena C, Cereda V, Remondo C, Gulley JL, Arlen PM, Pastan I, Schlom J, Tsang KY. Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4). Int. J. Cancer. 121: 595-605, 2007. [Journal] Gulley JL, Dahut WL. Future directions in tumor immunotherapy: CTLA4 blockade. Nature clinical practice. Oncology. 4: 136-7, 2007. [Journal] O'Mahony D, Morris JC, Quinn C, Gao W, Wilson WH, Gause B, Pittaluga S, Neelapu S, Brown M, Fleisher TA, Gulley JL, Schlom J, Nussenblatt R, Albert P, Davis TA, Lowy I, Petrus M, Waldmann TA, Janik JE. A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin. Cancer Res. 13: 958-64, 2007. [Journal] Wu SL, Jones E, Gulley JL, Arlen PM, Chen CC, Figg WD, Dahut WL. Routine interval computed tomography to detect new soft-tissue disease might be unnecessary in patients with androgen-independent prostate cancer and metastasis only to bone. BJU Int. 99: 525-8, 2007. [Journal] Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert opinion on biological therapy. 7: 543-54, 2007. [Journal] Arlen PM, Pazdur M, Skarupa L, Rauckhorst M, Gulley JL. A randomized phase II study of docetaxel alone or in combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229). Clin. Breast Cancer. 7: 176-9, 2006. [Journal] Ahlers CM, Camphausen K, Citrin D, Arlen PM, Gulley JL. A pilot trial of a carcinoembryonic antigen/ TRICOM-based vaccine and radiation to liver metastases in patients with carcinoembryonic antigen-positive solid tumors. Clinical colorectal cancer. 6: 72-5, 2006. [Journal] Tarassoff CP, Arlen PM, Gulley JL. Therapeutic vaccines for prostate cancer. Oncologist. 11: 451-62, 2006. [Journal] Madan RA, Gulley JL, Arlen PM. PSA-based vaccines for the treatment of prostate cancer. Expert review of vaccines. 5: 199-209, 2006. [Journal] Arlen PM, Dahut WL, Gulley JL. Immunotherapy for prostate cancer: what's the future?. Hematol. Oncol. Clin. North Am. 20: 965-83, xi, 2006. [Journal] Menard C, Johann D, Lowenthal M, Muanza T, Sproull M, Ross S, Gulley J, Petricoin E, Coleman C, Whiteley G, Liotta L, Camphausen K. Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis. Cancer Res. 66: 1844-50, 2006. [Journal] Gulley J, Figg W, Dahut W. Even more cost savings?. J Oncol Pract. 25: 202, 2006. [Journal] Lattouf JB, Arlen PM, Pinto PA, Gulley JL. A phase I feasibility study of an intraprostatic prostate-specific antigen-based vaccine in patients with prostate cancer with local failure after radiation therapy or clinical progression on androgen-deprivation therapy in the absence of local definitive therapy. Clinical genitourinary cancer. 5: 89-92, 2006. [Journal] Gulley JL, Parnes HL, Wright J, Dahut WL. Early treatment gets the benefit [letter]. J. Clin. Oncol. 24: 5172-3; author reply 5173, 2006. [Journal] Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin. Cancer Res. 12: 1260-9, 2006. [Journal] Garnett CT, Greiner JW, Tsang KY, Kudo-Saito C, Grosenbach DW, Chakraborty M, Gulley JL, Arlen PM, Schlom J, Hodge JW. TRICOM vector based cancer vaccines. Curr. Pharm. Des. 12: 351-61, 2006. [Journal] Dahut WL, Lakhani NJ, Gulley JL, Arlen PM, Kohn EC, Kotz H, McNally D, Parr A, Nguyen D, Yang SX, Steinberg SM, Venitz J, Sparreboom A, Figg WD. Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors. Cancer Biol. Ther. 5: 22-7, 2006. [Journal] Hodge JW, Greiner JW, Tsang KY, Sabzevari H, Kudo-Saito C, Grosenbach DW, Gulley JL, Arlen PM, Marshall JL, Panicali D, Schlom J. Costimulatory molecules as adjuvants for immunotherapy. Front. Biosci. 11: 788-803, 2006. [Journal