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Optimization of an innovative approach to eliminate CD70-positive cancer-associated fibroblasts to improve first-line chemotherapy in advanced colorectal cancer.
Cancer-associated fibroblasts (CAFs) provide a physical barrier for the delivery of systemic therapy to the tumor, making it an attractive target to combine with conventional treatment. Clinically addressing CAFs has been challenging due to its heterogeneous nature with both cancer-promoting and -restraining features. We have recently identified a distinct subset of CAFs in colorectal cancer specimens, marked by the expression of immune checkpoint CD70, and associated with a grim prognosis for the patient. Interestingly, CD70 is absent from normal epithelial tissue making it a safe target to eradicate the tumor-promoting CAFs. Therefore, the primary objective of the proposed translational research project is to develop a safe, effective cell-based strategy to eliminate CD70-positive cancer-associated fibroblasts. The secondary objective of the project is to rationally design and to preclinically evaluate a combination regimen of CD70-targeted therapy with first-line chemotherapy as a novel treatment option for patients with advanced CRC. Since we have also found CD70 expression in pancreatic cancer, this study can also pave the way to application in other malignancies.
Date:1 Apr 2019 → 30 Mar 2020
Keywords:CANCER ASSOCIATED FIBROBLASTS, CANCER IMMUNOTHERAPY, T-CELL ACTIVATION