Immune Response to the Carcinoembryonic Antigen in Patients Treated with an Anti-Idiotype Antibody Vaccine

Authors

Kenneth A. Foon, University of Kentucky
Mala Chakraborty, University of Kentucky
William J. John, University of Kentucky
Amanda Sherratt, University of Kentucky
Heinz Köhler, University of KentuckyFollow
Malaya Bhattacharya-Chatterjee, University of Kentucky

Abstract

We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; some cases were confirmed by immunoprecipitation of purified CEA. We also demonstrated Ab3 stained both autologous and allogeneic colonic tumors. 7 of 12 patients demonstrated idiotype specific T cell proliferative responses and four also showed T cell proliferation to CEA. Toxicity was limited to local reaction with mild fever and chills. All 12 patients eventually progressed after finishing 4-13 dosages. This is the first report demonstrating that a vaccine therapy is capable of breaking "immune tolerance" to CEA in patients with CEA positive tumors. Future studies will focus on treating patients with minimal residual disease.

Document Type

Article

Publication Date

7-1995

Notes/Citation Information

Published in The Journal of Clinical Investigation, v. 96, no. 1.

© The American Society for Clinical Investigation, Inc.

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)

https://doi.org/10.1172/JCI118039

Funding Information

This work was supported by National Institutes of Health grant P01- CA 57165.

Repository Citation

Foon, Kenneth A.; Chakraborty, Mala; John, William J.; Sherratt, Amanda; Köhler, Heinz; and Bhattacharya-Chatterjee, Malaya, "Immune Response to the Carcinoembryonic Antigen in Patients Treated with an Anti-Idiotype Antibody Vaccine" (1995). Markey Cancer Center Faculty Publications. 167.
https://uknowledge.uky.edu/markey_facpub/167