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. Virtual Clinical Trials Online This virtual event will bring together industry experts to discuss the increasing pace of pharmaceutical innovation, the need to maintain data quality and integrity as new technologies are implemented and understand regulatory challenges to ensure compliance. 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.
Xyphos Biosciences has partnered with The Parker Institute for Cancer Immunotherapy to improve the safety and effectiveness of first-generation CAR-T therapies. Xyphos has engineered the NKG2D receptor inactive until a bispecific is administered, enabling the NKG2D receptor to bind to a tumour antigen. Xyphos' method could also be used when mutating cancer cells render them unable to recognise their own antigens or other foreign proteins.