Modulation of T-Cell Activation in an Experimental Model of Mammary Carcinoma
Abstract
The goal of this research project was to study the requirements for T cell activation in generating a potent anti-tumor immune response. In the first year, using a transplantable mammary carcinoma model, we demonstrated that the combination of CTLA-4 blockade and a GM-CSF-expressing vaccine was effective for treatment of recently established tumors. This funded year, these findings were to be expanded to 2 additional models: a transplantable melanoma model and a primary prostate cancer model, resulting in one manuscript recently published (1), and one submitted (2). In the melanoma model, we demonstrated that CTLA-4 blockade, in combination with a GM-CSF-expressing vaccine, could eradicate both sub- cutaneous tumors as well as lung metastases. More strikingly, mice that rejected tumors underwent a progressive depigmentation, reminiscent of the vitiligo that occurs in melanoma patients undergoing immunotherapy (3). In the transgenic prostate cancer model, we demonstrated that primary, autoch- thonous prostate tumor incidence is reduced and the histologic severity of tumor lesions is reduced in mice treated with anti-CTLA-4 and a tumor cell vaccine. Interestingly, similarly treated, non-transgenic mice developed a destructive prostatitis. Taken together, our findings demonstrate the potency of this approach: by combining these synergistic therapies, both a potent anti-tumor and autoimmune response can occur. Future studies will address the link between tumor immunity and autoimmunity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA380385
Entities
People
- Arthur A. Hurwitz
Organizations
- University of California, Berkeley