Children's Hospital of Philadelphia Researchers Develop New Tool with Potential to Advance Precision Medicine Treatment for Cancer

Technology Discovers Antigen-Reactive T Cell Receptors with High Efficiency

PHILADELPHIA, Jan. 3, 2025 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania  developed a new screening technology, Aptamer-based T Lymphocyte Activity Screening and SEQuencing (ATLAS-seq), to better identify antigen-reactive T cells that are more likely to offer greater immune responses against cancer cells. The findings were reported this week in the journal Nature Communications.

Researchers continuously work to develop immunotherapy treatments that help the immune system recognize and attack specific protein targets on cancer cells, also known as tumor antigens, thereby training the body to fight cancer more effectively and precisely. Discovering antigen-reactive T cell receptors (TCRs) is essential to this precision medicine approach.

TCRs are protein complexes located on the surface of T cells that recognize and bind to antigen peptides presented by major histocompatibility complex (MHC) molecules, triggering a cascade of cellular responses that lead to T cell activation. However, standard methods for isolating antigen-reactive TCRs often fail to identify TCRs that effectively activate T cells.

"TCRs identified by ATLAS-seq tend to be more efficient in target cell killing than those identified by conventional technologies," said Lan Lin, PhD, senior author of the study and Assistant Professor in Pathology and Laboratory Medicine at Children's Hospital of Philadelphia and Penn Medicine. "Overall, ATLAS-seq improves TCR screening to more effectively identify antigen-reactive TCRs with high functional activity."

The ATLAS-seq technology combines a single-cell approach with an aptamer-based fluorescent molecular sensor that emits a fluorescence signal when a T cell is activated. In the study, the researchers designed a microfluidic system to isolate individual T cells that react to stimulation by an antigen peptide of interest and determined their unique TCR sequences using single-cell sequencing.

"We envision that ATLAS-seq can play a pivotal role in identifying TCRs targeting tumor antigens, driving the development of novel T cell immunotherapies for a broad range of hard-to-treat cancers," said Lin, who is also a researcher in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics and the Center for Computational and Genomic Medicine at CHOP.

This work was supported by National Institutes of Health grant R01GM121827, W.W. Smith Charitable Trust grant C2004 and a CHOP Research Institute Cell & Gene Therapy Collaborative seed grant.

Luo et al. "ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs." Nat Commun. January 2, 2025. DOI:10.1038/s41467-024-54675-3.

About Children's Hospital of Philadelphia: 
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu. 

Contact: Jennifer Lee
Children's Hospital of Philadelphia
(267) 426-6084
leej41@chop.edu

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SOURCE Children's Hospital of Philadelphia