Development of Hemichannel-Targeting Antibody Therapies for Breast Cancer Bone Metastasis
Abstract
The long-term goal of our research is to develop a first-in-class therapy in the treatment of breast cancer bone metastasis. Our central hypothesis is the activation of Cx43 hemichannels in osteocytes by antibody lead to the suppression of metastatic breast cancer in bone. We propose to develop a new antibody immunotherapy for breast cancer bone metastasis, reduce the disease-associated symptoms and improve overall survival rate of the patients. We developed a monoclonal antibody (mAb2)against Cx43 that activates Cx43 hemichannels in osteocytes and inhibits breast cancer bone invasion and growth in mouse models. During our first year of this award, we conducted comprehensive examination of the therapeutic potency of mAb2 as proposed in the Specific Aim 1 in subtypes of breast cancer using intracardiac and syngeneic bone metastatic models. Data obtained suggests mAb2 not only reduces the chance of tumor metastasizing to bone tissue, but greatly improves life span. Additionally, the reduction of tumor growth in bone was also observed not only in triple negative breast cancer, but also in an ER-positive breast cancer model. In some cases, long term treatment of mAb2 leads to total tumor regression. Moreover, administration of mAb2 enhanced immunity by increasing populations of T lymphocytes known to suppress tumor. Taken together, these data establish the efficacy of mAb2 when administrated systematically.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1093879
Entities
People
- Zhiqiang An
Organizations
- University of Texas Health Science Center at Houston