The study was 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.
American Gene Technologies International Inc. (AGT), a leading gene and cell therapy company, announced receipt of a second immuno-oncology patent on the stimulation of gamma delta T cells for treating solid tumors in epithelial cancers.
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 ImmunoTox lentivirus vector platform modifies tumor cells to greatly exaggerate the gamma delta T cell danger signal and to cascading response causes 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 invading cancer and raising their tumor-destruction activity both at the site of the treated primary tumor and abscopal against secondary tumors and metastases.
Gamma delta T cells have not been linked to autoimmunity. 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, but 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 might 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.
"Our understanding of how we can manipulate the immune system to treat poorly-responding cancers has made great strides over the past ten years. Most of this work was directed toward the adaptive immune system and finding ways to make CD8+ T cells more aggressive," said C. David Pauza, Ph.D., AGT's Chief Science Officer.