Enhancing the Effectiveness of Breast Cancer Immunotherapy Through Manipulation of the T Cell Cytoskeleton
Abstract
A limitation of adoptive immunotherapy is the poor survival and tumor localization of activated T cells after infusion. This problem arises in part from the polarized, adhesive form of activated T cells, which makes them prone to embolize in microvasculature. We hypothesized that transient inhibition of T cell polarization, induced just before infusion, will improve the survival and circulation of activated T cells. We found previously that T cells can be depolarized by the myosin light-chain kinase inhibitor ML-7. During the first project year we developed an ML-7 pretreatment protocol which depolarized activated T cells for 1 - 2 hr, then allowed them to recover normal cytotoxicity and proliferation within 24 hi. Initial experiments indicated that this protocol increased fourfold the homing of ErbB2-specific T cells to the ErbB2-expressing murine mammary tumor D2F2/E2. We have now confirmed this finding and tested whether the improved localization increased therapeutic effects. ML-7 pretreatment was found neither to enhance nor reduce the tumor-delaying effects of T cell infusion. This work is the first proof that cytoskeletal alteration of T cells can improve their trafficking behavior. Our first test, however, could not confirm that this strategy alone is enough to enhance adoptive immunotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421062
Entities
People
- Stuart Ratner
Organizations
- Wayne State University