The incidence of breast cancer, a common cause of death in women, is steadily increasing and patients with recurrent disease have a poor prognosis. This project proposes to develop a new therapeutic approach to breast cancer involving the use of monoclonal anti-idiotype (Id) antibodies as antigen substitutes to induce to anti-tumor response. We have recently generated and characterized a monoclonal anti-Id antibody, termed 1D10, which mimics biologically and antigenically a distinct and specific epitope of the high MW human milk fat globule (HMFG) primarily expressed at high density by human breast cancer and some other tumor cells. This epitope is identified by the mAb designated MC-10 or BrE1. MC-10 was used as the immunizing antibody or Ab1 to which anti-ld or Ab2 was generated. The antigenic determinant as defined by the mAbMC-10 (Ab1) and represented by 11D10 or Ab2 is minimally expressed on few normal adult tissues by immunoperoxidase staining and is absent on hematopoietic cells including granulocytes and platelets by flow cytometry analysis. Ab2, 11D10 or anti- Id was used to induce tumor specific antibodies in mice, rabbits and monkeys. Also, monoclonal anti-anti Ids or Ab3 which bind to HMFG Ag have been obtained from mice immunized with 11D10. Studies proposed here will use alum precipitated anti-Id 11D10 to actively immunize patients with MC- 1- positive breast cancer in a phase 1b clinical trial during year 1-2. The objectives of this study are 1) to determine the effects of a single monoclonal anti-Id antibody precipitated with alum, on humoral and cellular immunity; 2) to determine the ability of patients to generate Ab3 (Ab1') response and cytolytic T lymphocytes (CTL) specific for autologous and/or allogeneic tumor cells; 3) to determine the overall anti-murine antibody response to the anti-idiotype antibody; 4) to determine the optimal immunomodulatory dose of the anti0Id antibody; and 5) to monitor clinical responses. These studies will assist in identification of the criteria for optimal immunization and selection of patients who may benefit from anti- idiotype vaccine therapy. At the completion of the Phase 1b trial, we plan to begin a Phase II trial in year 2-3 using the optimum immunomodulatory dose. In year 4 we will initiate a Phase 1lb clinical trial with the selected anti-Id 11K10-cytokine fusion protein developed and tested in Research Project (RP) II.
| 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 |
| Tripathi, P K; Qin, H; Bhattacharya-Chatterjee, M et al. (1999) Construction and characterization of a chimeric fusion protein consisting of an anti-idiotype antibody mimicking a breast cancer-associated antigen and the cytokine GM-CSF. Hybridoma 18:193-202 |
