By attaching a bispecific T-cell engager (BiTE) protein to an oncolytic virus called enadenotucirev, scientists have devised a dual action approach to target many carcinomas.
Dr. Nathan Richardson, head of molecular and cellular medicine at the Medical Research Council noted that: “Immunotherapy is emerging as an exciting new approach to treating cancers. This innovative viral delivery system, which targets both the cancer and surrounding protective tissue, could improve outcomes for patients whose cancers are resistant to current treatments.
Cancer is a complex disease that can take advantage of the connective tissue surrounding organs, stromal cells, in order to avoid detection and siphon nutrients and growth factors. The BiTE vaccine was designed to bind the two cells together so that the immune system kills both the abnormal cells and affected fibroblasts in one move.
Details about the procedure were published in the latest edition of the Cancer Research journal in an article describing how the team managed to cause cancer cells to produce a BiTE response – binding fibroblast activation protein on cancer-associated fibroblasts (CAF), but also to CD3ε on T cells, leading to potent T-cell activation and fibroblast death.
“Treatment of fresh clinical biopsies, including malignant ascites and solid prostate cancer tissue, with FAP-BiTE–encoding virus-induced activation of tumor-infiltrating PD1+ T cells to kill CAFs. In ascites, this led to depletion of CAF-associated immunosuppressive factors, upregulation of proinflammatory cytokines, and increased gene expression of markers of antigen presentation, T-cell function, and trafficking. M2-like ascites macrophages exhibited a proinflammatory repolarization, indicating spectrum-wide alteration of the tumor microenvironment”.
A number of clinical trials are underway testing doses and possible side effects.
Dr. Kerry Fisher from the Department of Oncology at the University of Oxford added that “Our new technique to simultaneously target the fibroblasts while killing cancer cells with the virus could be an important step towards reducing immune system suppression within carcinomas and should kick-start the normal immune process”.