Relapse after HSCT 2021 | Advances in off-the-shelf CAR T-cells
Catherine Bollard, MBChB, MD, FRACP, FRCPA, Children’s National Health System, Washington, DC, outlines studies exploring the potential use of allogeneic or ‘off-the-shelf’ chimeric antigen receptor (CAR) T-cell products. Although their safety profile is currently not comparable to viral-specific T-cells (VSTs), Prof. Bollard reports that a study has recently used CAR-transduced third party VSTs as an off-the-shelf therapy for lymphoma. In addition, CAR-transduced natural killer (NK) cells have shown tolerable safety across multiple platforms and have effectively been used to prevent post-transplant relapse in patients with acute myeloid leukemia. This interview took place at the 2021 Relapse After HSCT² Workshop in New York, NY.
Transcript (edited for clarity)
So, the challenges to overcome with CAR therapies or CAR T-cell therapies in particular is really to see if we can move beyond the patient-specific model and leveraging what we’ve learned from the VST space, being able to go off-the-shelf safely in the largest part in that setting, how can we get to off-the-shelf CAR T-cell therapies. And several groups have looked at different gene engineering strategies to knock down the native alpha/beta TCR, but so far it has not been the same home run in terms of safety profile that we’ve seen with the third party VSTs...
So, the challenges to overcome with CAR therapies or CAR T-cell therapies in particular is really to see if we can move beyond the patient-specific model and leveraging what we’ve learned from the VST space, being able to go off-the-shelf safely in the largest part in that setting, how can we get to off-the-shelf CAR T-cell therapies. And several groups have looked at different gene engineering strategies to knock down the native alpha/beta TCR, but so far it has not been the same home run in terms of safety profile that we’ve seen with the third party VSTs.
So, people are looking at other platforms on to which you can transduce the CARs. So, one interesting platform is to actually transduce your third-party VSTs. And there’s a study ongoing at Baylor where they using, off-the-shelf EBV specific T-cells that are transduced with a CAR to use as an off-the-shelf therapy for lymphoma. So, that’s really capitalizing on the safety of the off-the-shelf virus-specific T-cell platform to use the CAR. And then there’s a lot of interest, obviously around the use of CAR-transduced NK cells or natural killer cells, which have been used safely across multiple platforms in the non-transduced setting, using-off-the shelf NK cells, especially for the prevention of relapse of AML after transplant.
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Disclosures
Catherine Bollard, MBChB, MD, FRACP, FRCPA, is the Co-founder and scientific advisory board member of Catamaran Bio and Mana Therapeutics, is a board member of Cabaletta Bio, owns stock in Neximmune, Repertoire Immune Medicines and DSMB- SOBI; and participates in advisory boards for Pfizer, BMS and Roche on an ad hoc basis.
