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New test to determine whether CAR T-Cell therapy will work for lymphoma patients

Sept 2022: According to a study published in the Journal of Clinical Investigation, an engineer at the University of Houston (UH) may have discovered a mechanism to identify which lymphoma patients are most likely to respond to chimeric antigen receptor (CAR) T-cell therapy.

Physicians can expedite treatment and maybe save more lives if they are aware of which lymphoma patients react to CAR T-cell therapy. On the other hand, sharing light on people who react poorly and experience serious side effects can open up more possibilities for alternative treatments.

Researchers found a special connection between the T cell protein CD2 and the cancer receptor CD58 in their investigations.

In the tumours of lymphoma patients who benefit more from CAR T-cell therapy, the CD2 ligand CD58 is expressed at higher levels, according to study author Navin Varadarajan, PhD, MD Anderson professor of chemical and biomolecular engineering.

A T cell’s CD2 protein is bound by CD58. When CD58 activates CD2, the protein changes into a molecule that can obliterate cancer cells on contact.

According to certain recent studies, cancer can be treated by using the patient’s own biological system. One particular technique, called CAR T-cell therapy, modifies T cells in the lab so that they will fight cancer cells once they have returned to the body. The consequences of this life-saving procedure could linger for ten years or longer.

In order to conduct a more thorough investigation into the connection between CD58 and CD2, Varadarajan collaborated with a research team from The University of Texas MD Anderson Cancer Center.

Varadarajan collaborated with Sattva Neelapu (MD Anderson) to stain patient tumours prior to CAR T treatment and examine cell expression using the TIMING (Timelapse Imaging Microscopy In Nanowell Grids) technique that Varadarajan developed in his lab. This high-throughput single-cell technology can assess how cells move, activate, kill, survive, and interact.

The scientists discovered that tumours expressing higher amounts of the cancer receptor CD58 responded better to CAR T-cell therapy based on the hundreds of interactions they saw between T cells and tumour cells using TIMING.

Varadarajan stated in the news announcement, “We found that CD2 on T cells is related with directional migration. Death and serial killing are accelerated by the interaction between CD2 on T cells and CD58 on lymphoma cells.

Varadarajan is aiming to commercialise the TIMING technique. He co-founded the UH-based business CellChorus. Patients may submit CellChorus their target cells on an individual basis; these cells will be examined using the TIMING test; this service is not yet accessible to professionals.

In the press release, Varadarajan said, “We are extremely fortunate to have the Technology Bridge as our incubator location in Houston, next to the nation’s top medical facility, with unique access to the centres of medicine difficult to replicate in most other cities in the country.

Dr Nishant Mittal
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Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.

Research Highlights

Dr. Mittal's research has focused on several key areas:

1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.

2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.

4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.

Publications and Presentations

Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.

In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.

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  • September 3rd, 2022

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