This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by von Mehren, M. Articles by Weiner, L. M. Search for Related Content PubMed PubMed Citation Articles by von Mehren, M. Articles by Weiner, L. M.

Pilot Study of a Dual Gene Recombinant Avipox Vaccine Containing Both Carcinoembryonic Antigen (CEA) and B7.1 Transgenes in Patients with Recurrent CEA-expressing Adenocarcinomas¹

Departments of Medical Oncology [M. v. M., N. M., M. D., S. M., L. M. W.], Biostatistics [A. R.], and Pathology [H. S. C.], Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, and Laboratory of Tumor Immunology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [P. A., K. Y. T., J. S.]

Coordinated presentation of antigen and costimulatory molecules has been shown to result in the induction of an antigen-specific T-cell response rather than the development of anergy. This study evaluated the vaccine ALVAC-CEA B7.1, a canary pox virus that has been engineered to encode the gene for the tumor-associated antigen carcinoembryonic antigen (CEA) and B7.1, a T-cell costimulatory molecule. Patients with CEA-expressing tumors were immunized with 2.5 x 10⁷ (n = 3), 1.0 x 10⁸ (n = 6), and 4.5 x 10⁸ (n = 30) plaque-forming units intradermally every other week for 8 weeks. Patients with stable or responding disease received monthly boost injections. Biopsies of vaccine sites were obtained 48 h after vaccination to evaluate leukocytic infiltration and CEA expression. Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-. Therapy was well tolerated, without significant toxicity attributable to vaccine. All patients had evidence of leukocytic infiltration and CEA expression in vaccine biopsy sites. Six patients with elevated serum CEA values at baseline had declines in their levels lasting 4–12 weeks. These patients all had stable disease after four vaccinations. After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA- specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline. The number of prior chemotherapy regimens was inversely correlated with the ability to generate a T-cell response. ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, and it is associated with the induction of a CEA-specific T-cell response.

This article has been cited by other articles:

				S. Kim-Schulze, H. S. Kim, A. Wainstein, D. W. Kim, W. C. Yang, D. Moroziewicz, P. Y. Mong, M. Bereta, B. Taback, Q. Wang, et al. Intrarectal Vaccination with Recombinant Vaccinia Virus Expressing Carcinoembronic Antigen Induces Mucosal and Systemic Immunity and Prevents Progression of Colorectal Cancer J. Immunol., December 1, 2008; 181(11): 8112 - 8119. [Abstract] [Full Text] [PDF]

				H. L. Kaufman, H.-J. Lenz, J. Marshall, D. Singh, C. Garett, C. Cripps, M. Moore, M. von Mehren, R. Dalfen, W. J. Heim, et al. Combination Chemotherapy and ALVAC-CEA/B7.1 Vaccine in Patients with Metastatic Colorectal Cancer Clin. Cancer Res., August 1, 2008; 14(15): 4843 - 4849. [Abstract] [Full Text] [PDF]

				J. Schlom, J. L. Gulley, and P. M. Arlen Paradigm Shifts in Cancer Vaccine Therapy Experimental Biology and Medicine, May 1, 2008; 233(5): 522 - 534. [Abstract] [Full Text] [PDF]

				T. I. Naslund, C. Uyttenhove, E. K. L. Nordstrom, D. Colau, G. Warnier, M. Jondal, B. J. Van den Eynde, and P. Liljestrom Comparative Prime-Boost Vaccinations Using Semliki Forest Virus, Adenovirus, and ALVAC Vectors Demonstrate Differences in the Generation of a Protective Central Memory CTL Response against the P815 Tumor J. Immunol., June 1, 2007; 178(11): 6761 - 6769. [Abstract] [Full Text] [PDF]

				R. H. Wilson Novel Therapeutic Developments Other Than EGFR and VEGF Inhibition in Colorectal Cancer Oncologist, October 1, 2006; 11(9): 1018 - 1024. [Abstract] [Full Text] [PDF]

				D. Nagorsen and E. Thiel Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Clin. Cancer Res., May 15, 2006; 12(10): 3064 - 3069. [Abstract] [Full Text] [PDF]

				S. Dai, T. Wan, B. Wang, X. Zhou, F. Xiu, T. Chen, Y. Wu, and X. Cao More Efficient Induction of HLA-A*0201-Restricted and Carcinoembryonic Antigen (CEA)-Specific CTL Response by Immunization with Exosomes Prepared from Heat-Stressed CEA-Positive Tumor Cells Clin. Cancer Res., October 15, 2005; 11(20): 7554 - 7563. [Abstract] [Full Text] [PDF]

				S. Mosolits, G. Ullenhag, and H. Mellstedt Therapeutic vaccination in patients with gastrointestinal malignancies. A review of immunological and clinical results Ann. Onc., June 1, 2005; 16(6): 847 - 862. [Abstract] [Full Text] [PDF]

				M. G. Cusi, M. T. Del Vecchio, C. Terrosi, G. G. Savellini, G. Di Genova, M. La Placa, F. Fallarino, C. Moser, C. Cardone, G. Giorgi, et al. Immune-Reconstituted Influenza Virosome Containing CD40L Gene Enhances the Immunological and Protective Activity of a Carcinoembryonic Antigen Anticancer Vaccine J. Immunol., June 1, 2005; 174(11): 7210 - 7216. [Abstract] [Full Text] [PDF]

				J. L. Marshall, J. L. Gulley, P. M. Arlen, P. K. Beetham, K.-Y. Tsang, R. Slack, J. W. Hodge, S. Doren, D. W. Grosenbach, J. Hwang, et al. Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen-Expressing Carcinomas J. Clin. Oncol., February 1, 2005; 23(4): 720 - 731. [Abstract] [Full Text] [PDF]

				H. L. Kaufman Integrating Bench With Bedside: The Role of Vaccine Therapy in the Treatment of Solid Tumors J. Clin. Oncol., February 1, 2005; 23(4): 659 - 661. [Full Text] [PDF]

				C. T. Garnett, C. Palena, M. Chakarborty, K.-Y. Tsang, J. Schlom, and J. W. Hodge Sublethal Irradiation of Human Tumor Cells Modulates Phenotype Resulting in Enhanced Killing by Cytotoxic T Lymphocytes Cancer Res., November 1, 2004; 64(21): 7985 - 7994. [Abstract] [Full Text] [PDF]

				L. E. Raez, P. A. Cassileth, J. J. Schlesselman, K. Sridhar, S. Padmanabhan, E. Z. Fisher, P. A. Baldie, and E. R. Podack Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., July 15, 2004; 22(14): 2800 - 2807. [Abstract] [Full Text] [PDF]

				H. E. Zeytin, A. C. Patel, C. J. Rogers, D. Canter, S. D. Hursting, J. Schlom, and J. W. Greiner Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice Cancer Res., May 15, 2004; 64(10): 3668 - 3678. [Abstract] [Full Text] [PDF]

				G. J. Ullenhag, J.-E. Frodin, S. Mosolits, S. Kiaii, M. Hassan, M. C. Bonnet, P. Moingeon, H. Mellstedt, and H. Rabbani Immunization of Colorectal Carcinoma Patients with a Recombinant Canarypox Virus Expressing the Tumor Antigen Ep-CAM/KSA (ALVAC-KSA) and Granulocyte Macrophage Colony- stimulating Factor Induced a Tumor-specific Cellular Immune Response Clin. Cancer Res., July 1, 2003; 9(7): 2447 - 2456. [Abstract] [Full Text] [PDF]

				C. Palena, J. Schlom, and K.-Y. Tsang Differential Gene Expression Profiles in a Human T-cell Line Stimulated with a Tumor-associated Self-peptide versus an Enhancer Agonist Peptide Clin. Cancer Res., May 1, 2003; 9(5): 1616 - 1627. [Abstract] [Full Text] [PDF]

				J. W. Greiner, H. Zeytin, M. R. Anver, and J. Schlom Vaccine-based Therapy Directed against Carcinoembryonic Antigen Demonstrates Antitumor Activity on Spontaneous Intestinal Tumors in the Absence of Autoimmunity Cancer Res., December 1, 2002; 62(23): 6944 - 6951. [Abstract] [Full Text] [PDF]

				E. S. Kass, J. W. Greiner, J. A. Kantor, K. Y. Tsang, F. Guadagni, Z. Chen, B. Clark, R. D. Pascalis, J. Schlom, and C. Van Waes Carcinoembryonic Antigen as a Target for Specific Antitumor Immunotherapy of Head and Neck Cancer Cancer Res., September 1, 2002; 62(17): 5049 - 5057. [Abstract] [Full Text] [PDF]

				J. Schmitz, E. Reali, J. W. Hodge, A. Patel, G. Davis, J. Schlom, and J. W. Greiner Identification of an Interferon-{gamma}-inducible Carcinoembryonic Antigen (CEA) CD8+ T-Cell Epitope, Which Mediates Tumor Killing in CEA Transgenic Mice Cancer Res., September 1, 2002; 62(17): 5058 - 5064. [Abstract] [Full Text] [PDF]

				N. L. Berinstein Carcinoembryonic Antigen as a Target for Therapeutic Anticancer Vaccines: A Review J. Clin. Oncol., April 15, 2002; 20(8): 2197 - 2207. [Abstract] [Full Text] [PDF]

				H. Horig, A. Wainstein, L. Long, D. Kahn, S. Soni, A. Marcus, W. Edelmann, R. Kucherlapati, and H. L. Kaufman A New Mouse Model for Evaluating the Immunotherapy of Human Colorectal Cancer Cancer Res., December 1, 2001; 61(23): 8520 - 8526. [Abstract] [Full Text] [PDF]

				D. W. Grosenbach, J. C. Barrientos, J. Schlom, and J. W. Hodge Synergy of Vaccine Strategies to Amplify Antigen-specific Immune Responses and Antitumor Effects Cancer Res., June 1, 2001; 61(11): 4497 - 4505. [Abstract] [Full Text] [PDF]

				M. von Mehren, P. Arlen, J. Gulley, A. Rogatko, H. S. Cooper, N. J. Meropol, R. K. Alpaugh, M. Davey, S. McLaughlin, M. T. Beard, et al. The Influence of Granulocyte Macrophage Colony-Stimulating Factor and Prior Chemotherapy on the Immunological Response to a Vaccine (ALVAC-CEA B7.1) in Patients with Metastatic Carcinoma Clin. Cancer Res., May 1, 2001; 7(5): 1181 - 1191. [Abstract] [Full Text]