Our long term goal is to develop novel therapeutic vaccines for cancer patients using internal image anti-idiotype (Id) antibody, which is based on the immune network hypothesis of Jerne. Our anti-Id, 3H1, which resembles an epitope of the carcinoembryonic antigen (CEA), acts as a surrogate for CEA, and we have completed a phase Ib trial of colon cancer patients with this anti-Id. In this trial, we have demonstrated the development of anti-CEA immune responses in 3H1 treated patients. the goal of this project is to design """"""""second generation"""""""" anti-Id vaccines to enhance the humoral and cellular immunogenicity of 3H1. For this purpose, we will make DNA vaccines based on the structure of 3H1. Variable domains of heavy and light chains of an antibody molecule stabilized by a linker is the smallest antibody fragment (scFv) capable of binding an antigen. Plasmids and recombinant vaccinia virus capable of expressing 3H1 scFv in eukaryotic cells will be the DNA vaccines. Recent studies have shown that inoculation of plasmid DNA encoding a variety of proteins leads to T cell and antibody responses in vivo against these proteins. Vaccinia virus is highly immunogenic and stimulates both humoral and cell-mediated immune responses. Co- presentation of this surrogate antigen and vaccinia viral antigens is likely to enhance the anti-tumor immunity in tumor bearing hosts. We will evaluate the potential for these vaccines in a syngeneic mouse tumor model expressing transduced CEA and study the mechanism of anti-tumor immunity induced by these DNA vaccines. This study will be a prelude to a clinical trial for colorectal cancer patients with second generation anti-Id based DNA vaccines.
| Bhattacharya-Chatterjee, Malaya; Chatterjee, Sunil K; Foon, Kenneth A (2002) Anti-idiotype antibody vaccine therapy for cancer. Expert Opin Biol Ther 2:869-81 |
| Bhattacharya-Chatterjee, M; Chatterjee, S K; Foon, K A (2001) The anti-idiotype vaccines for immunotherapy. Curr Opin Mol Ther 3:63-9 |
| Zeytin, H E; Tripathi, P K; Bhattacharya-Chatterjee, M et al. (2000) Construction and characterization of DNA vaccines encoding the single-chain variable fragment of the anti-idiotype antibody 1A7 mimicking the tumor-associated antigen disialoganglioside GD2. Cancer Gene Ther 7:1426-36 |
| Chatterjee, S K; Tripathi, P K; Chakraborty, M et al. (1998) Molecular mimicry of carcinoembryonic antigen by peptides derived from the structure of an anti-idiotype antibody. Cancer Res 58:1217-24 |
| Tripathi, P K; Qin, H; Deng, S et al. (1998) Antigen mimicry by an anti-idiotypic antibody single chain variable fragment. Mol Immunol 35:853-63 |
