T cell attacking cancer cell, illustration

Researchers at University of Texas at Arlington are developing a tiny nanopore system to trap antigens so doctors can order highly personalized cancer therapies. The team is developing a method to use even very small samples to find peptide-presenting major histocompatility complex (MHC ) receptors and determine which T-cell receptor-like antibodies (TCRmABs) could improve a patient’s response to particular cancer therapies.

The work is being led by George Alexandrakis, bioengineering professor, who just received a $250,000 Cancer Prevention and Research Institute of Texas (CPRIT) grant. The grant is titled “Ultrasensitive Nanosensor-Based Detection of Tumor Immunogenic Peptides to Enable Personalized Cancer Immunotherapy.”

Cancer treatment has been transformed by the introduction of targeted drugs and checkpoint inhibitors. While cancer immunotherapy is be very promising, one drawback has been how relatively few patients respond to these drugs. For checkpoint inhibitors, it is estimated that between 15% to 20% of patients respond.

T-cells, which originate in the thymus, are immune cells that help protect the body from infection and foreign particles, but can also attack cancer cells if they recognize them as foreign. A major current challenge is that cancer cells can mask themselves to appear as healthy cells.

Alexandrakis’ team is developing a plasmonic nanosensor-based system to quantify the number of peptide-presenting MHC ligands that are targeted by TCRmABs. To avoid needing to grow biopsied cells in cultures, their goal is to use only a few thousand cancer cells per assay, from tissue or blood.

“One of the challenges with cancer is that it is so variable. It changes all the time and is different in all people,” Alexandrakis said. “This research will use sensors we’ve developed to see what it is the T-cells are being attracted to when they decide to invade a tumor. The sensors are sniffing out what is there that the T-cells have noticed that activated them and made them ready to fight. This will enable us in the future to design a personalized, time-sensitive treatment.”

The tail region of TCR-like mAbs, Alexandrakis points out, can be modified to help attract the patient’s immune cells against the cancer. Thus, further personalizing the treatment.

The technique his team are using employs an optical trapping mechanism of proteins by nanoholes drilled in gold and known as “self-induced back-action,” or SIBA. They create a SIBA actuated nanopore electrophoresis (SANE) sensor by combining optical trapping with a vertically directed voltage that pushes proteins through the center of the nanohole.

“This project can lay a foundation for immunotherapy that will work more specifically for an individual patient and would revolutionize cancer treatment as we know it,” said Michael Cho, chair of the UT Arlington Department of Bioengineering.

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