This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foon, K. A. Articles by Bhattacharya-Chatterjee, M. Search for Related Content PubMed PubMed Citation Articles by Foon, K. A. Articles by Bhattacharya-Chatterjee, M. Social Bookmarking                            What's this?

Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen

From the Division of Hematology/Oncology, Department of Internal Medicine, and Barrett Cancer Center for Prevention, Treatment and Research, University of Cincinnati Medical Center, Cincinnati, and Oncology Hematology Care, Inc, Cincinnati, OH; Division of Hematology/Oncology, Department of Internal Medicine, and Lucille Parker Markey Cancer Center, University of Kentucky Medical Center, Lexington, KY; Titan Pharmaceuticals, Inc, South San Francisco, CA; and Aquila Biopharmacueticals, Framingham, MA.

Address reprint requests to Kenneth A. Foon, MD, Barrett Cancer Center, 234 Goodman St, ML 0502 Room 1097, Cincinnati, OH 45219-2316; emailkenneth.foon{at}uc.edu

PURPOSE: We generated an anti-idiotype antibody, designated CeaVac, that is an internal image of the carcinoembryonic antigen (CEA). We previously demonstrated that the majority of patients with advanced colorectal cancer generate specific anti-CEA responses. The purpose of the current study was to treat patients with surgically resected colon cancer with CeaVac to determine the immune response and clinical outcome to treatment with vaccine. We also compared the immune responses between patients treated with fluorouracil (5-FU) chemotherapy regimens plus vaccine versus vaccine alone.

PATIENTS AND METHODS: Thirty-two patients with resected Dukes' B, C, and D, and incompletely resected Dukes' D disease were treated with 2 mg of CeaVac every other week for four injections and then monthly until tumor recurrence or progression. Fourteen patients were treated concurrently with 5-FU chemotherapy regimens.

RESULTS: All 32 patients entered onto this trial generated high-titer immunoglobulin G and T-cell proliferative immune responses against CEA. The 5-FU regimens did not have a qualitative or quantitative effect on the immune response. Three of 15 patients with Dukes' B and C disease progressed at 19, 24, and 35 months. Seven of eight patients with completely resected Dukes' D disease remained on study from 12 to 33 months; one patient with resected Dukes' D disease relapsed at 9 months. One patient with incompletely resected Dukes' D disease remained on study at 14 months without evidence of progression; eight experienced disease progression at 6 to 31 months.

CONCLUSION: CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. R. Parkhurst, J. Joo, J. P. Riley, Z. Yu, Y. Li, P. F. Robbins, and S. A. Rosenberg Characterization of Genetically Modified T-Cell Receptors that Recognize the CEA:691-699 Peptide in the Context of HLA-A2.1 on Human Colorectal Cancer Cells Clin. Cancer Res., January 1, 2009; 15(1): 169 - 180. [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]

				M. C. Posner, D. Niedzwiecki, A. P. Venook, D. R. Hollis, H. L. Kindler, E. W. Martin, R. L. Schilsky, R. M. Goldberg, and for the Cancer and Leukemia Group B A Phase II Prospective Multi-institutional Trial of Adjuvant Active Specific Immunotherapy Following Curative Resection of Colorectal Cancer Hepatic Metastases: Cancer and Leukemia Group B Study 89903 Ann. Surg. Oncol., January 1, 2008; 15(1): 158 - 164. [Abstract] [Full Text] [PDF]

				J. Schlom, P. M. Arlen, and J. L. Gulley Immunotherapies with Other Therapeutic Modalities: New Paradigms for Clinical Trial Design ASCO Educational Book, January 1, 2008; 2008(1): 101 - 106. [Abstract] [Full Text] [PDF]

				P. Sabbatini and K. Odunsi Immunologic Approaches to Ovarian Cancer Treatment J. Clin. Oncol., July 10, 2007; 25(20): 2884 - 2893. [Abstract] [Full Text] [PDF]

				J. Schlom, P. M. Arlen, and J. L. Gulley Cancer Vaccines: Moving Beyond Current Paradigms Clin. Cancer Res., July 1, 2007; 13(13): 3776 - 3782. [Abstract] [Full Text] [PDF]

				G. J. Ullenhag, I. Spendlove, N. F.S. Watson, A. A. Indar, M. Dube, R. A. Robins, C. Maxwell-Armstrong, J. H. Scholefield, and L. G. Durrant A Neoadjuvant/Adjuvant Randomized Trial of Colorectal Cancer Patients Vaccinated with an Anti-Idiotypic Antibody, 105AD7, Mimicking CD55 Clin. Cancer Res., December 15, 2006; 12(24): 7389 - 7396. [Abstract] [Full Text] [PDF]

				J Pfisterer, A du Bois, J Sehouli, S Loibl, S Reinartz, A Reuss, U Canzler, A Belau, C Jackisch, R Kimmig, et al. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann. Onc., October 1, 2006; 17(10): 1568 - 1577. [Abstract] [Full Text] [PDF]

				G. Chong, A. Bhatnagar, D. Cunningham, T. M. Cosgriff, P. G. Harper, W. Steward, J. Bridgewater, M. Moore, J. Cassidy, R. Coleman, et al. Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer Ann. Onc., March 1, 2006; 17(3): 437 - 442. [Abstract] [Full Text] [PDF]

				P. M. Arlen, J. L. Gulley, C. Parker, L. Skarupa, M. Pazdur, D. Panicali, P. Beetham, K. Y. Tsang, D. W. Grosenbach, J. Feldman, et al. A Randomized Phase II Study of Concurrent Docetaxel Plus Vaccine Versus Vaccine Alone in Metastatic Androgen-Independent Prostate Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1260 - 1269. [Abstract] [Full Text] [PDF]

				S. Y. Chui, T. M. Clay, H. K. Lyerly, and M. A. Morse The Development of Therapeutic and Preventive Vaccines for Gastric Cancer and Helicobacter pylori Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 1883 - 1889. [Abstract] [Full Text] [PDF]

				X. Wang, E. C. Ko, L. Peng, S. D. Gillies, and S. Ferrone Human High Molecular Weight Melanoma-Associated Antigen Mimicry by Mouse Anti-Idiotypic Monoclonal Antibody MK2-23: Enhancement of Immunogenicity of Anti-Idiotypic Monoclonal Antibody MK2-23 by Fusion with Interleukin 2 Cancer Res., August 1, 2005; 65(15): 6976 - 6983. [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]

				C. Schwegler, A. Dorn-Beineke, S. Nittka, C. Stocking, and M. Neumaier Monoclonal Anti-idiotype Antibody 6G6.C4 Fused to GM-CSF Is Capable of Breaking Tolerance to Carcinoembryonic Antigen (CEA) in CEA-Transgenic Mice Cancer Res., March 1, 2005; 65(5): 1925 - 1933. [Abstract] [Full Text] [PDF]

				W. W.L. Choi, S. Srivatsa, and J. C. Ritchie Aberrant Thyroid Testing Results in a Clinically Euthyroid Patient Who Had Received a Tumor Vaccine Clin. Chem., March 1, 2005; 51(3): 673 - 675. [Full Text] [PDF]

				A. Saha, S. K. Chatterjee, K. A. Foon, F. J. Primus, S. Sreedharan, K. Mohanty, and M. Bhattacharya-Chatterjee Dendritic Cells Pulsed with an Anti-Idiotype Antibody Mimicking Carcinoembryonic Antigen (CEA) Can Reverse Immunological Tolerance to CEA and Induce Antitumor Immunity in CEA Transgenic Mice Cancer Res., July 15, 2004; 64(14): 4995 - 5003. [Abstract] [Full Text] [PDF]

				G. J. Ullenhag, J.-E. Frodin, M. Jeddi-Tehrani, K. Strigard, E. Eriksson, A. Samanci, A. Choudhury, B. Nilsson, E. D. Rossmann, S. Mosolits, et al. Durable Carcinoembryonic Antigen (CEA)-Specific Humoral and Cellular Immune Responses in Colorectal Carcinoma Patients Vaccinated with Recombinant CEA and Granulocyte/Macrophage Colony-Stimulating Factor Clin. Cancer Res., May 15, 2004; 10(10): 3273 - 3281. [Abstract] [Full Text] [PDF]

				S. Reinartz, S. Kohler, H. Schlebusch, K. Krista, P. Giffels, K. Renke, J. Huober, V. Mobus, R. Kreienberg, A. duBois, et al. Vaccination of Patients with Advanced Ovarian Carcinoma with the Anti-Idiotype ACA125: Immunological Response and Survival (Phase Ib/II) Clin. Cancer Res., March 1, 2004; 10(5): 1580 - 1587. [Abstract] [Full Text] [PDF]

				M. Lomas, W. Liauw, D. Packham, K. Williams, A. Kelleher, J. Zaunders, and R. Ward Phase I clinical trial of a human idiotypic p53 vaccine in patients with advanced malignancy Ann. Onc., February 1, 2004; 15(2): 324 - 329. [Abstract] [Full Text] [PDF]

				R L Jones, D Cunningham, G Cook, and P J Ell Tumour vaccine associated lymphadenopathy and false positive positron emission tomography scan changes Br. J. Radiol., January 1, 2004; 77(913): 74 - 75. [Abstract] [Full Text] [PDF]

				C. Casati, P. Dalerba, L. Rivoltini, G. Gallino, P. Deho, F. Rini, F. Belli, D. Mezzanzanica, A. Costa, S. Andreola, et al. The Apoptosis Inhibitor Protein Survivin Induces Tumor-specific CD8+ and CD4+ T Cells in Colorectal Cancer Patients Cancer Res., August 1, 2003; 63(15): 4507 - 4515. [Abstract] [Full Text] [PDF]

				B. K. Ko, K. Kawano, J. L. Murray, M. L. Disis, C. L. Efferson, H. M. Kuerer, G. E. Peoples, and C. G. Ioannides Clinical Studies of Vaccines Targeting Breast Cancer Clin. Cancer Res., August 1, 2003; 9(9): 3222 - 3234. [Abstract] [Full Text] [PDF]

				S. Reinartz, A. Hombach, S. Kohler, H. Schlebusch, D. Wallwiener, H. Abken, and U. Wagner Interleukin-6 Fused to an Anti-idiotype Antibody in a Vaccine Increases the Specific Humoral Immune Response against CA125+ (MUC-16) Ovarian Cancer Cancer Res., June 15, 2003; 63(12): 3234 - 3240. [Abstract] [Full Text] [PDF]

				A. Saha, S. K. Chatterjee, K. A. Foon, F. J. Primus, and M. Bhattacharya-Chatterjee Murine Dendritic Cells Pulsed with an Anti-Idiotype Antibody Induce Antigen-specific Protective Antitumor Immunity Cancer Res., June 1, 2003; 63(11): 2844 - 2854. [Abstract] [Full Text] [PDF]

				G. Pentheroudakis and N. Pavlidis Immunomodulation in colorectal cancer: disappointment or promise? Ann. Onc., March 1, 2003; 14(3): 349 - 351. [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]

				G. J. Ullenhag, J.-E. Frodin, K. Strigard, H. Mellstedt, and C. G. M. Magnusson Induction of IgG Subclass Responses in Colorectal Carcinoma Patients Vaccinated with Recombinant Carcinoembryonic Antigen Cancer Res., March 1, 2002; 62(5): 1364 - 1369. [Abstract] [Full Text] [PDF]

				N. Habal, R. K. Gupta, A. J. Bilchik, R. Yee, Z. Leopoldo, W. Ye, R. M. Elashoff, and D. L. Morton CancerVax, An Allogeneic Tumor Cell Vaccine, Induces Specific Humoral and Cellular Immune Responses in Advanced Colon Cancer Ann. Surg. Oncol., June 1, 2001; 8(5): 389 - 401. [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]

				K. A. Foon and M. Bhattacharya-Chatterjee Are Solid Tumor Anti-Idiotype Vaccines Ready for Prime Time?: Commentary re: U. Wagner et al., Immunological Consolidation of Ovarian Carcinoma Recurrences with Monoclonal Anti-Idiotype Antibody ACA125: Immune Responses and Survival in Palliative Treatment. Clin. Cancer Res., 7: 1154-1162, 2001. Clin. Cancer Res., May 1, 2001; 7(5): 1112 - 1115. [Full Text]

				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]

				K. A. Foon, J. Lutzky, R. N. Baral, J. R. Yannelli, L. Hutchins, A. Teitelbaum, O. L. Kashala, R. Das, J. Garrison, R. A. Reisfeld, et al. Clinical and Immune Responses in Advanced Melanoma Patients Immunized With an Anti-Idiotype Antibody Mimicking Disialoganglioside GD2 J. Clin. Oncol., January 14, 2000; 18(2): 376 - 376. [Abstract] [Full Text] [PDF]

				R. M. Conry, K. O. Allen, S.-w. Lee, S. E. Moore, D. R. Shaw, and A. F. LoBuglio Human Autoantibodies to Carcinoembryonic Antigen (CEA) Induced by a Vaccinia-CEA Vaccine Clin. Cancer Res., January 1, 2000; 6(1): 34 - 41. [Abstract] [Full Text]