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Armoured CAR ‘could overwhelm solid tumour resistance’

Eureka Therapeutics and Memorial Sloan Kettering approach shows promise

A souped-up version of chimeric antigen receptor (CAR) T-cell therapy has shown it can improve the targeting of solid tumours.

CARs are already on the market for blood cancers where getting access to the malignant cells is much easier, but solid tumours are considered a tougher proposition as they are tougher to penetrate and tend to be swamped with immunosuppressive factors. Making CARs that also express PD-1 checkpoint inhibitors – what researchers call an “armoured CAR” – could be the solution, according to a study published in Nature Biotechnology.

Memorial Sloan Kettering Cancer Center's Renier Brentiens

The study looked at two armoured CARs in animal models – one targeting CD19-positive cells (the target of approved CAR-Ts for B-cell cancers from Novartis and Kite/Gilead) and a second directed at MUC-16 antigens which are found on some ovarian and pancreatic cancers.

The study showed CAR-T cells that co-expressed the PD-1 inhibitor were more likely to stay locally around the tumour site, and persisted there for longer. Moreover, the PD-1 inhibitor seemed to help recruit nearby T-cells to fight the cancer, and overall the effects seemed to be as effective or superior to giving a regular CAR-T alongside a systemic PD-1-blocking antibodies. The approach would also minimise any systemic side effects from giving PD-1 drugs.

The armoured CARs enhanced the survival of the mice, according to the authors, who conclude that “this strategy has the potential to enhance the efficacy of CAR-T cell therapy in cancers with an immune-suppressive TME” (tumour microenvironment).

“These data, together with in vivo models, suggest that this is an early step toward exploring how we can make the first iterations of CAR-T-cell therapies even better,” said Brentjens.

The approach was developed in collaboration with US biotech Eureka Therapeutics, which provided the technology needed to develop the PD-1 antibody component. Eureka and Memorial Sloan Kettering have been working together on T-cell therapies since 2013.

Cheng Liu

The company’s chief executive Cheng Liu (pictured above) who is a co-author of the Nature paper, said he is excited about applying the PD-1 antibody strategy to Eureka’s ARTEMIS T-cell receptor platform, designed to create CAR-Ts that are less likely to cause cytokine-related side effects than currently-approved therapies.

Article by
Phil Taylor

17th August 2018

From: Research

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