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Cellectis publishes description of new ‘all-in-one’ CAR-T architecture

Cellectis publishes description of new ‘all-in-one’ CAR-T architecture

T-cells attacking cancer cell illustration of microscopic photosT-cells attacking cancer cell illustration of microscopic photos

One of the companies developing CAR-T therapies that don’t require patients to have their own T cells harvested has developed an architecture that it said could streamline manufacturing and improve safety.

French biotech firm Cellectis said Tuesday that it had published a study describing the development of CubiCAR, an “all-in-one” architecture that embeds a multi-function tag for purification, detection and elimination. The company said the architecture combines multiple functions into one molecule that is also compatible with multiple proteins called single-chain variable fragments designed against different targets, giving it the potential to make CAR-Ts safer.

While they have demonstrated a high degree of efficacy, CAR-T therapies in blood cancers have also long had issues with safety, in particular potentially fatal side effects like cytokine release syndrome (CRS) – a type of allergic reaction – and neurological side effects.

For example, bluebird bio presented data at the American Society of Clinical Oncology’s annual meeting in Chicago – which concluded last week – of its multiple myeloma CAR-T, bb2121, showing that nearly all the patients who got the highest dose responded to therapy. Among all 43 patients in the study, 63 percent experienced cytokine release syndrome, with a small minority experiencing it at the level normally requiring hospitalization, and 33 percent experienced neurotoxicity. The two approved CAR-T therapies, namely Novartis’ Kymriah and Gilead Sciences’ Yescarta, have also been known to cause CRS and neurotoxicity. CRS is often treated using Roche’s rheumatoid arthritis drug Actemra.

With respect to manufacturing, at the Biotechnology Innovation Organization’s annual conference, which also ended last week, experts pointed out that a big question that remains for CAR-Ts is whether manufacturers can handle the volume that will come as therapies move into greater commercial development. Part of the challenge will be not only manufacturing the therapies in higher quantities, but doing so in a manner that ensures patients can quickly receive them.

Cellectis is developing several allogeneic CAR-Ts. Unlike Kymriah, Yescarta and bb2121, allogeneic CAR-Ts are “off-the-shelf” therapies and do not require harvesting the patient’s own T cells for shipping to a central plant and processing before the finished product is shipped back for infusion. Another company, Belgium-based Celyad, is also developing allogeneic CAR-Ts. Another potential player is Swiss firm CRISPR Therapeutics, which is using CRISPR-Cas9 gene-editing technology to develop allogeneic CAR-T therapies. However, CRISPR-Cas9 ran into trouble this week with the publication of two papers indicating it may risk causing tumors.

Originally posted on MedCityNews.com

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