Treatment of Breast Cancer with Antibodies Against DR4 and DR5 Receptors in Combination with Chemotherapy
Abstract
The overall goal of this proposal is to determine the therapeutic potential of apoptosis-inducing anti-human DR5 and DR4 antibodies, alone or together, in combination with chemotherapeutic drugs with activity against breast cancer, for the treatment of metastatic breast cancer. Aim 1 was to determine the expression profile in human breast cancer cell lines of DR5 and DR4 before and after treatment with anti-DR5 and -DR4 MAb alone, together, and in combination with chemotherapy drugs. Aim 3 was to determine the cytotoxicity of anti-DR5 and -DR4 antibodies against human breast cancer cells alone, together, and in combination with adriamycin or paclitaxel. Aim 4 was to determine the therapeutic efficacy and toxicity of anti-DR5 and -DR4 antibodies against human breast cancer xenografts alone, together, and combined with adriamycin or paclitaxel. All breast cancer cell lines expressed DR5 with TRA-8 reactivity varying from strongly to weakly positive. Four cell lines were sensitive to TRA-8 cytotoxicity with IC(50) of 17 to 299 ng/ml while other cell lines had weak cytotoxicity or were resistant. In vivo studies demonstrated significant inhibition of growth of 2LMP xenografts by TRA-8 treatment alone. TRA-8 alone or in combination with adriamycin, paclitaxel, or radiation produced a significant increase in tumor doubling time compared to any modality alone. Complete tumor regressions occurred in 1/42 untreated animals, 1/54 animals receiving chemotherapy and/or radiation and 28/68 animals receiving TRA-8 alone or TRA-8 combination regimens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418338
Entities
People
- Donald J. Buchsbaum
Organizations
- University of Alabama