Current screening methods do not give an accurate indication of CAR T efficacy in vivo

Watch our webinar where Marcela Maus shows that cell avidity is a highly predictive biomarker

Recent research findings uproot the current ways used to select CAR variants for cancer therapies while presenting a new, highly predictive biomarker. This research shows how current in vitro screening methods do not accurately predict in vivo efficacy, where as cell avidity does. Learn more about this groundbreaking change in our webinar with Dr. Marcela Maus.

Watch our Nature webinar!

In this webinar, Dr. Marcela Maus, Associate Professor at Harvard Medical School and Director of Cellular Immunotherapy at the Massachusetts General Hospital, presents her recent work (published in Cancer Cell and Nature) on the generation of productive CARs and how cell avidity measurements render this possible for solid and liquid tumors.

Research Highlights from Leick et al. 2022 in Cancer Cell

Marcel Maus and team reveal cell avidity as the best predictive biomarker for in vivo tumor control.
In addition, the researchers present “avidity enhancement” as a promising strategy for efficient CAR-T design against acute myeloid leukemia (AML).

Scientific Highlights:

  • Enhanced tumor clearance in AML mouse models results from enhancing the binding avidity on both sides of the synapse, by engineering more stable CD27-based CARs and pharmacologically increasing CD70 antigen density on AML cells
  • CAR-T cell avidity variants highly correlated with in vivo tumor eradication efficiency (R=0.906), in high contrast to  in vitro cytotoxicity (R=0.598) and cytokine secretion (R=0.548) assays (Figure 1).

Figure 1 Graphs show correlation between 3 in vitro measurements of CAR T-cell potency (cytotoxicity, IFNƴ secretion, and avidity) and their anti-tumor effect in mice as a goodness-of-fit-R2 values. Data from Leick et al. 2022, Figure 5H.

Key Insights

Leick et al. tested various CAR variants with different in vitro methods and subsequently in AML mouse models, looking for the best functioning CAR to develop further. They found that cytokine secretion and cytotoxicity assays often cannot differentiate between the different CAR constructs and even favor contrasting variants, as previously described by the lab of Hinrich Abken (Chmielewski et al. 2004).

Notably, in vivo, neither of the favored variants was effective in tumor killing. However, researchers still rely on these assays to select CAR Ts for further clinical studies.

Consider how this lack of correlation impacts your drug discovery time and costs?

Using the z-Movi Cell Avidity Analyzer, Leick and colleagues were able to differentiate between all CAR variants based on their avidity to target cells (Figure 2). Most importantly, avidity values were highly predictive of in vivo tumor eradication (Figure 1 and 3).

Why use the z-Movi?

Because it is the only tool that allows you to reliably select the best CAR variants, saving you invaluable time and costs.

Find out more about the z-Movi here.

z-Movi<sup>®</sup> High-throughput Label-free Cell Interaction Studies

Get exclusive access to the webinar with Marcela Maus

Watch our webinar to get new insights into successful CAR-T engineering by the CAR expert Dr. Marcela Maus. Learn about cell avidity – a promising novel biomarker that is highly predictive of in vivo tumor killing – and how Dr. Maus uses it in her pioneering research.

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