Skip to main content

Cell Avidity: a superior predictor of in vivo efficacy of CAR-T cells

Part of: CAR T cells

Cell Avidity: a superior predictor of in vivo efficacy of CAR-T cells

NEW: Cell Avidity identified the poor clinical efficacy of the APRIL CAR-T cell therapy

In a recent JITC paper named  “Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T cell therapy’’  published by the team of Dr. Lydia Lee, cell avidity successfully identified the issue behind the poor clinical efficacy of the APRIL CAR shown during an unsuccessful phase I clinical trial to treat multiple myeloma while traditional in vitro assays failed to pinpoint the issue (Figure 1).

Cell avidity enabled researchers to establish poor tumor binding (or avidity) by cell bound APRIL compared to competitor FDA approved CARs (Figure 2) as a likely explanation providing an improved preclinical readout that can predict efficacy in patients.

Key takeaways:

  • APRIL CAR had significantly reduced binding to BCMA-expressing target cells, ranking the lowest among the FDA-approved clinical CARs (bb2121 and LCAR).
  • This deficiency in binding contributed to the APRIL CAR’s poor performance in the phase I clinical trial.
  • Incorporating cell avidity would have allowed for more informed decision-making, potentially leading to the selection of a different lead candidate or optimizing the APRIL CAR design before its clinical trial deployment
Download the white paper

Figure 1 Phase I clinical trial of APRIL CAR-T cells in patients with refractory MM resulted in poor clinical outcome.

Figure 2 Cell avidity between CAR transduced T cells from 4 healthy donors and myeloma cell line H929 gated at 1000 pN. Multiple paired T tests and Holm Sidak correction *p<0.05, **p<0.01, ***p<0.001.

Dr. Lydia Lee

University College London
Group Leader Cell Therapy

‘’In this unique exploration of the reasons underpinning suboptimal clinical responses in the AUTO2 trial, the LUMICKS platform allowed us to establish poor tumour binding (or avidity) by cell bound APRIL compared to competitor CARs as a likely explanation. Only with such studies will the field acquire a greater understanding of the key preclinical readouts that can predict efficacy in patients.’’

Data courtesy of Dr. Lydia Lee

Traditional screening methods give an inaccurate indication of CAR T efficacy in vivo

Recent research findings from Dr. Marcela Maus’ group 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.

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.

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.

Download the application note

Figure 1 Cell avidity measurement accurately predicts in vivo tumor control. Cell avidity measurement proved to be more accurate than other standard assays used to characterize CARs, such as in vitro cytotoxicity and cytokine secretion.

Watch our Nature webinar!

Webinars Marcela Maus

Cell Avidity Measurements to Understand and Enhance CAR-T/Tumor Interactions in Acute Myeloid Leukemia

Dr. Marcela Maus used avidity measurements to understand and enhance productive CAR-T cell interactions.

Watch on demand
Data courtesy of Dr. Marcela V. Maus at Harvard Medical School

Solid tumors avoid CAR T cell killing through cell avidity escape

CAR T cell therapies have been transformative in battling blood-related cancers; however, the more prevalent solid tumors have been less responsive to this therapeutic approach. This study aimed to investigate the mechanisms involved in solid tumor escape of CAR T cell therapies. By screening several glioblastoma cell lines, including ones derived from patients, the team of Dr. Marcela V. Maus found that loss of genes in the interferon-γ receptor (IFNγR) signaling pathway (IFNGR1, JAK1 or JAK2) rendered them more resistant to CAR T cell killing. Similar results were observed in vivo in IFNγR knockout mouse models.

Transcriptional profiling of IFNγR knockout (KO) cells showed a lower upregulation of cell-adhesion molecules after exposure to CAR T cells, leading to reduced cell avidity (Figure 2A) and reduced CAR T cell killing. This, ultimately, resulted in solid tumor escape. The avidity escape resistance mechanism to CAR T cell killing was further established by showing that ICAM-1 overexpression in IFNγR1 KO cells restored cell avidity.

Download the application note

Figure 2 Cell avidity accurately predicts CAR T cell killing ability in solid tumors. Reduced avidity between IFNγR1 KO and CAR T cells, as measured with the z-Movi Cell Avidity Analyzer

Watch our Nature webinar!

Webinars Rebecca Larson

Cell avidity as a crucial biomarker for CAR T response

Dr. Rebecca Larson’s work revealed important evasion mechanism from CAR T cell response in solid tumors.

Watch on demand
Data courtesy of Dr. Marcela V. Maus at Harvard Medical School

Our solutions

Cell avidity as a service

Cell Avidity analysis can be performed at high throughput using our services platform, enabling the screening of hundreds of CAR-T cells to rapidly find the most potent CAR-T for in vivo testing. 

Dr. Rogier Reijmers
Principal Scientist at LUMICKS

Download the brochure to learn more

Join our mailing list

I would like to receive exclusive news about the latest product developments, dynamic single-molecule and immuno-oncology events and breakthrough science. I can revoke my consent at any time.

By submitting the form you agree to LUMICKS' privacy policy.

Close Menu

For pricing, reach out to your application scientist or account manager

Open Email

Fill in our contact form, we will reach out to you!

Please include ‘Lakeview data analysis price inquiry’ in the Message box

Contact Us

Join our newsletter

Get exclusive news on the latest publications, product developments, events and breakthrough science.

By submitting the form you agree to LUMICKS' privacy policy. You can revoke your consent at any time.

Download our webinar recording:


Download our Cell Therapy (CAR-T, TCR, NK) applications deck