New Test Helps Determine Whether CAR T-Cell Therapy Will Work for Lymphoma Patients

An engineer at the University of Houston (UH) may have found a method to determine which patients with lymphoma are most likely to respond to chimeric antigen receptor (CAR) T-cell therapy, according to a study published in the Journal of Clinical Investigation.

With knowledge of which lymphoma patients respond to CAR T-cell therapy, physicians can hasten the treatment process and possibly save more lives. Conversely, shedding light on patients who respond poorly with severe adverse effects can provide a better window for alternative treatment options.

In their studies, researchers observed a unique relationship between the cancer ligand CD58 and the T cell protein CD2.

“The ligand for CD2, CD58 is expressed at higher levels in the tumors of lymphoma patients who respond better to CAR T-cell treatment,” said study lead Navin Varadarajan, PhD, MD Anderson professor of chemical and biomolecular engineering.

CD58 binds to the CD2 protein on a T cell. When CD58 activates CD2, it transforms the protein into a molecule that can directly kill cancer cells.

Some new cancer research shows that scientists can use a patient’s own biological system to fight cancer. One specific treatment, CAR T-cell therapy, alters T cells in the lab to attack cancer cells once they have re-entered the body. The effects of this lifesaving treatment could last 10 or more years.

Varadarajan worked with a research team from The University of Texas MD Anderson Cancer Center to study the relationship between CD58 and CD2 more in depth.

Using the TIMING (Timelapse Imaging Microscopy In Nanowell Grids) method that Varadarajan developed in his lab—a high-throughput single-cell technology that can evaluate how cells move, activate, kill, survive, and interact—Varadarajan worked with Sattva Neelapu (MD Anderson) to stain patient tumors before CAR T treatment and look at cell expression.

Based on the thousands of T cell and tumor cell interactions they observed using TIMING, the team found that tumors expressing higher levels of cancer ligand CD58 responded better to CAR T-cell therapy.

“We identified that CD2 on T cells is associated with directional migration,” Varadarajan said in the press release. “The interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing.”

Varadarajan, who co-founded the UH-based company CellChorus, is working on commercializing the TIMING process. Not yet available to clinicians, patients can individually send CellChorus their target cells, which will be analyzed using the TIMING test.

“We are so lucky to have the Technology Bridge as our incubator space in Houston, near the greatest medical center in the country, with unique access to the centers of medicine difficult to replicate in most other places in the country,” Varadarajan concluded in the press release.

Reference

University of Houston. Technology developed at UH could advance treatment of lymphoma. August 24, 2022. Accessed on August 24, 2022. https://www.eurekalert.org/news-releases/962748