ATLAS technology, by Genocea Biosciences, may be a useful tool to identify specific molecules in cancer patients that can help develop personalized vaccines, according to new research.
These findings result from a collaborative effort between Genocea and researchers atMemorial Sloan Kettering Cancer Center (MSK), and were recently presented in a poster at the 31st annual meeting of the Society for Immunotherapy of Cancer (SITC), that recently concluded in Maryland.
The poster was titled “Genome-Scale Neoantigen Using ATLASTM Prioritizes Candidates For Immunotherapy In A Non-Small Cell Lung Cancer Patient.”
The immune system is composed of several types of cells that fight off diseases, including T-cells. Pathogens or cancer cells express specific molecules (antigens) that are recognized by T-cells as ‘outsiders’, prompting an immune system attack to eliminate them. But not all antigens trigger T-cell surveillance, which is why the immune system sometimes fails to detect and fight certain diseases.
For this reason, knowing which antigens will activate a protective response by the T-cells, and which won’t, helps in designing appropriate vaccines to strengthen immune system activity.
ATLAS technology, the company reports in a news release, can both identify and distinguish between antigens that favor the immune system against disease and those that don’t. By associating each patient’s T-cell response signatures with different clinical outcomes, ATLAS is designed to select the most clinically relevant antigens (those that elicit protective T-cell responses) to be used in the development of new vaccines.
Researchers used the ATLAS technology to unravel clinically meaningful antigens in one patient with non-small cell lung cancer (NSCLC), successfully treated with the PD-1 inhibitor Keytruda (pembrolizumab). ATLAS used the patient’s own T-cells to screen a set of 103 patient-specific tumor mutations, allowing researchers to identify which antigens were possibly contributing to an anti-tumor response in this patient.
The technology identified several antigens to which the patient’s T-cells could respond to kill a tumor. This, the company reported, was an important finding, as many antigens had not been discovered using other methods, such as predictive computer algorithms.
“These data are the first evidence that personalized neoantigens can be comprehensively identified using functional evidence of T cell responses through ATLAS,” Jessica Baker Flechtner, PhD and chief scientific officer at Genocea, said in the release. “The differences between neoantigens identified by ATLAS and those noted by standard predictive algorithms reinforces the weaknesses of these algorithms and the potential for ATLAS to find better neoantigens. We believe that by improving antigen selection we can develop more effective cancer vaccines.”
As the ATLAS technology allows a global understanding of a patient’s immune response to cancer, it is possible to detect which antigen candidates will stimulate a productive T-cell response and which will be associated with an inhibitory immune response.
“These findings support the hypothesis that next-generation personalized T cell immunotherapies with biologically evidenced neoantigens may improve outcomes for patients for whom current therapies are ineffective,” said Timothy Chan, MD, PhD, one of the senior authors of the study.
Future studies are warranted to further validate these results.
