Parker Institute teams up with Xyphos to tame CAR-Ts

handshake over a desk with computers and someone taking notes
The billionaire-backed Parker Institute is investing in Xyphos and will help create and test preclinical CAR-T candidates. (rawpixel)

The Parker Institute for Cancer Immunotherapy has teamed up with Xyphos Biosciences to advance next-generation CAR-T therapies. Like others in the field, the Parker Institute and Xyphos are working to improve on the blunt force of the initial CAR-Ts by creating more controllable therapies free from the safety issues and efficacy limitations of their predecessors.

Xyphos is contributing CAR-T technology to the partnership. The biotech, which was created last year in the breakup of AvidBiotics, has engineered the NKG2D receptor to be inactive until it comes into contact with a bispecific. By using the engineered receptor in CAR-T therapies, Xyphos may be able create cells that circulate harmlessly when first administered. Xyphos could then turn the CAR-T on by administering a bispecific that binds to its inactive NKG2D receptor and a tumor antigen.

In theory, the approach has several advantages over first-generation CAR-Ts. The use of bispecifics to activate CAR-T therapies and bring them into contact with tumor cells could reduce off-target effects and enable modulation of the intensity of the treatment. In contrast, if first-generation CAR-Ts start proliferating dangerously quickly, physicians have limited ability to pump the brakes on the treatment.

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The other theoretical benefit relates to efficacy. Gilead’s Yescarta and Novartis’ Kymriah both target CD19. If cancer cells mutate to stop expressing the antigen, the first-generation CAR-Ts are rendered ineffective. Xyphos’ approach could counter this tumor defense mechanism. As the bispecifics serve as the targeting mechanism, Xyphos could respond to CD19 escape by delivering antibodies tuned to a different antigen. That way, the same CAR-Ts could be aimed at a sequence of different targets.

Xyphos is lagging behind biotechs that are working on different fixes for the same problems. Autolus is running a clinical trial of a CAR-T designed to tackle both the safety and efficacy concerns, in its case through a rituximab-activated off switch and dual-targeting mechanism. Other companies, such as Bellicum and Ziopharm, are working on safety switches, while Gilead acquired a synthetic biology startup to equip its CAR-Ts with control mechanisms.

We are still some way from finding out how these different approaches compare, but Xyphos is now better equipped to validate its approach. The billionaire-backed Parker Institute is investing in Xyphos and will help create and test preclinical CAR-T candidates based on the technology. 

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