Gene-Product Auto-Targeting to Tumor Vessels
Project Summary Treatment options are limited and prognosis is poor for patients with recurrent or metastatic sarcoma. Both soft tissue sarcoma and osteosarcoma most frequently metastasize to the lungs and are often resistant to cytotoxic chemotherapy. Novel treatment options such as immune therapy are urgently needed for long-term control and elimination of metastatic disease. In that regard, both T cell (CAR-T and TILs) therapy and immune checkpoint blocking therapy have advanced to clinical applications in other types of tumors. In fact, wildtype IL12-armed T (CAR- or TIL) cells is more powerful in eliminating tumors than T cells alone in both preclinical tumor model or clinical trial because IL12 polarize T cells to the Th1 phenotype, boost effector T cells, downregulate angiogenesis, remodel the extracellular matrix, and alter levels of immune-suppressive cytokines. One urgent challenge for either CAR-T or wildtype IL12-armed T cell therapy is adverse effects. The CAR-T cells caus