Complement Inhibition in the Immunotherapy of Breast Cancer
Abstract
Our studies demonstrated that blockade of the complement anaphylatoxin C5a receptor (C5aR) reduced tumor growth in syngeneic and Her2 transgenic mouse models of breast cancer. In both models the therapeutic efficacy of C5aR inhibitor was comparable to the efficacy of Listeria monocytogenes-delivered Her2 vaccine (Lm-LLO-Her2). Importantly, C5aR inhibition synergized with Lm-LLO-Her2 in limiting tumor growth. These therapeutic effects were associated with the enhanced recruitment of tumor-specific CD8+ T cells to tumors. Notably, C5aR inhibition alone contributed to this recruitment and induced tumor-specific T cell responses at the periphery. The induction of the robust anti-tumor T cell responses by various treatments resulted likely from the attenuation of tumor mediated immunosuppression, since we observed that Lm-LLO-Her2, C5aR inhibition and the combination of Lm-LLO-Her2 with C5aR inhibition reduced infiltration of tumors by myeloid-derived suppress cells (MDSCs). The C5aR blockade impacted MDSC infiltration of tumors more than Lm-LLO-Her2. Overall, our data indicate that complement inhibition can become a novel immunotherapy for breast cancer patients in a form of monotherapy or in the combination with other treatment modalities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2013
- Accession Number
- ADA580968
Entities
People
- Maciej Markiewski
Organizations
- Texas Tech University Health Sciences Center