Novel screening tech enhances identification of cancer-targeting T cell receptors

Researchers at Kids’s Hospital of Philadelphia (CHOP) and the Perelman College of Drugs on the College of Pennsylvania have developed a brand new screening know-how, Aptamer-based T Lymphocyte Exercise Screening and SEQuencing (ATLAS-seq), to raised determine antigen-reactive T cells which are extra more likely to provide higher immune responses in opposition to most cancers cells. The findings had been reported this week in Nature Communications.

Researchers constantly work to develop immunotherapy therapies that assist the immune system acknowledge and assault particular protein targets on most cancers cells, also called tumor antigens, thereby coaching the physique to battle most cancers extra successfully and exactly. Discovering antigen-reactive T cell receptors (TCRs) is crucial to this precision drugs method.

TCRs are protein complexes situated on the floor of T cells that acknowledge and bind to antigen peptides offered by main histocompatibility advanced (MHC) molecules, triggering a cascade of mobile responses that result in T cell activation. Nonetheless, commonplace strategies for isolating antigen-reactive TCRs typically fail to determine TCRs that successfully activate T cells.

“TCRs recognized by ATLAS-seq are usually extra environment friendly in goal cell killing than these recognized by standard applied sciences,” stated Lan Lin, Ph.D., senior creator of the research and Assistant Professor in Pathology and Laboratory Drugs at Kids’s Hospital of Philadelphia and Penn Drugs. “General, ATLAS-seq improves TCR screening to extra successfully determine antigen-reactive TCRs with excessive practical exercise.”

The ATLAS-seq know-how combines a single-cell method with an aptamer-based fluorescent molecular sensor that emits a fluorescence sign when a T cell is activated. Within the research, the researchers designed a microfluidic system to isolate particular person T cells that react to stimulation by an antigen peptide of curiosity and decided their distinctive TCR sequences utilizing single-cell sequencing.

“We envision that ATLAS-seq can play a pivotal function in figuring out TCRs concentrating on tumor antigens, driving the event of novel T cell immunotherapies for a broad vary of hard-to-treat cancers,” stated Lin, who can be a researcher within the Raymond G. Perelman Middle for Mobile and Molecular Therapeutics and the Middle for Computational and Genomic Drugs at CHOP.