Novel approach to activating gamma delta T cells shows promise in animal studies -- demonstrating efficacy in multiple epithelial solid tumors and metastases
American Gene Technologies International Inc. (AGT), a leading gene and cell therapy company, today announced receipt of a second immuno-oncology patent on the stimulation of gamma delta T cells for treating solid tumors in epithelial cancers. U.S. Patent No: 9,914,938 dated March 13, 2018 further consolidates AGT’s intellectual property position surrounding its novel gene therapy platform. The patent describes AGT’s unique lentivirus vector approach to modify tumors for potent activation of naturally-occurring T cells in the immune system providing a highly-effective immune response and destruction of tumors.
Gamma delta T cells are a class of T cells that recognize and attack a broad range of tumor types, including solid and liquid (hematologic) cancers. The most common form of gamma delta T cell in blood responds to changes in tumor cell metabolism and has exquisite ability to distinguish normal from malignant tissues. When gamma delta T cells contact tumor cells, they become activated and gain the capacity to kill tumor cells. AGT’s ImmunoToxTM lentivirus vector platform modifies tumor cells to greatly exaggerate the gamma delta T cell danger signal and a cascading response causes activated T cells to target both genetically-modified and unmodified tumor cells. AGT’s unique approach of “lighting up” the primary tumor leaves the gamma delta T cells in a completely natural state, while alerting them to the invading cancer and raising their tumor-destruction activity - both at the site of the treated primary tumor, and abscopally against secondary tumors and metastases. Gamma delta T cells have not been linked to auto-immunity. Some diseases cause gamma delta T cells to rise to become 50% or more of circulating T cells, as compared with 6% for a healthy system, without creating cytokine release syndrome. Consequently, it is believed that AGT’s approach is likely to be safe for a wide variety of solid tumors, including liver, pancreatic, prostate, breast, lung, ovarian, colon and others. Most tumor types can be modified by ImmunoTox to become highly stimulatory for gamma delta T cells to unleash a potent attack on malignant cells, yet the surrounding normal tissues are spared from damage by the highly-selective gamma delta T cells.
AGT’s ImmunoTox vector strategy seeks to fill critical gaps in current immuno-oncology approaches. Gamma delta T cells may be especially potent against solid tumors due to effective tumor infiltration and highly active tumor cell killing. The gamma delta T cell response does not require unique cell surface markers for each tumor, as is necessary for the development of chimeric antigen receptor T cells (CAR-T) or for monoclonal antibodies capable of targeting tumors. Gamma delta T cells also appear less sensitive to immune checkpoint inhibitors compared to other T cells. Importantly, ImmunoTox provides for local stimulation of gamma delta T cells that elicits a more targeted response with less systemic exposure to therapeutic agents. These characteristics speak to the tremendous potential for cancer immunotherapy using locally-activated, highly-specific gamma delta T cells.
“Our understanding of how we can manipulate the immune system to treat poorly-responding cancers has made great strides over the past 10 years,” commented C. David Pauza, Ph.D., AGT’s Chief Science Officer. “However, most of this work was directed toward the adaptive immune system and finding ways to make CD8+ T cells more aggressive in their attack on tumors. More recently there has been increased interest in employing the innate immune system, particularly gamma delta T cells, because of their exquisite ability to discriminate normal from malignant tissues and great capacity for killing a broad range of tumor types. We believe AGT is at the forefront of this trend with an approach that has demonstrated significant activity in animal models and holds promise for treating cancer without directly modifying the immune system. We look forward to continuing our in vivo work as we progress toward an IND and clinical trials.”
Jeff Galvin, AGT’s CEO added:
Gamma delta T cells have been gaining attention in biotech and Pharma as evidenced by recent collaborations announced by Bluebird Bio and Takeda to examine opportunities surrounding gamma delta T cells. Importantly, our platform is significantly differentiated and more advanced than these other programs -- one of which involves the permanent genetic modification of the cells in the manner of CAR-T. Our platform is designed to make tumor cells more immunogenic such that unmodified gamma delta T cells respond aggressively to the genetically-modified tumor cells as well as tumor cells at sites distant to the treated area. We look forward to advancing this program with the ultimate goal of providing oncologists and their patients with truly novel, efficacious and well-tolerated treatments for cancers.