On May 24, 2022 LUMICKS, a leading life science tools company that develops instruments for dynamic single-molecule and cell avidity analysis, reported the publication in Cancer Cell of preclinical research identifying "Avidity Enhancement" as a new strategy to improve therapeutic outcome of Chimeric Antigen Receptor (CAR) T cell immunotherapy in Acute Myeloid Leukemia (AML) (Press release, LUMICKS, MAY 24, 2022, View Source;utm_medium=rss&utm_campaign=avidity-enhancement-new-strategy-for-improving-car-t-therapy [SID1234614972]).

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AML poses significant clinical challenges due to its resistance to therapies and its bleak prognosis. Approximately 20,000 people in the US and 300,000 worldwide die from AML every year, making it the most common form of acute leukemia in adults and a major public health issue.

The Cancer Cell paper (May 9, 2022), entitled "Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia," was authored by a team of CAR T cell researchers led by Dr. Marcela V. Maus, Associate Professor of Medicine at Harvard Medical School and Director of the Cellular Immunotherapy program at Massachusetts General Hospital.

The study details a novel strategy for better cancer treatment with CAR T cells for AML. "Avidity Enhancement", increasing cell-cell binding from both the tumor and CAR T cell side, led to a more effective eradication of tumors in mouse models of AML. In this paper, data generated using the LUMICKS z-Movi Cell Avidity Analyzer provided superior correlation with CAR T cell activity in vivo compared to the standard in vitro assays in assessing the potency of CAR variants.

Building upon previous research from the Maus Lab indicating ‘avidity escape’ as an evasion mechanism when CAR T cell therapies are deployed against solid tumors, "avidity enhancement" is a promising strategy for improving clinical success of CAR T therapies.

"We continue to be excited about the pivotal research emerging from The Maus Lab and other leading laboratories that demonstrates how researchers can leverage the technological and scientific power of measuring cell avidity with the z-Movi Cell Avidity Analyzer," said Andrea Candelli, PhD, Chief Scientific Officer of LUMICKS. "This work further solidifies the idea that cell avidity can be a unique biomarker to improve the selection of CAR T therapies for superior therapeutic outcomes in hematological malignancies as well as in solid tumors. We are delighted to collaborate with researchers worldwide in uncovering meaningful new insights, such as the new treatment approaches suggested for AML contained in this new paper in Cancer Cell."

The z-Movi Cell Avidity Analyzer measures cell avidity, or level of binding, between immune cells and their targets, enabling researchers to identify the most potent immunotherapeutic effector cells. This unique technology provides predictive, reproducible, and fast results at single-cell resolution. LUMICKS’ cell avidity solutions use acoustics to measure forces and interactions between cells, with the goal of shortening the drug development cycle of immunotherapies and reducing failure rates in clinical trials. First introduced in 2020, the z-Movi is being rapidly adopted by academic and biopharma laboratories around the world.

About the Study Findings

Unlike other forms of leukemia, AML has been notoriously difficult to successfully target using CAR T cells. Researchers believe this is due to both low expression of the antigenic targeted protein on the cancer cells and unstable expression of activating receptors on the T cells.

In this publication, the researchers have shown that increasing avidity of the CAR T cells to their target cells leads to enhanced tumor killing in vitro as in mouse models. Target protein expression on the cancer cells was chemically enhanced using available therapeutics and/or changing the design of the CAR to stabilize its expression on the T cells. Through this method, the researchers show that enhancing cell avidity for therapeutic efficacy can be achieved by modulating the tumor cell or modulating the surface of the T cell. Either strategy increased the sensitivity of the tumor to CAR T mediated clearance, confirming cell avidity as a crucial biomarker in immune oncology.