Targeting immune checkpoints is a well-established strategy in cancer therapy, and antibodies blocking PD-1/PD-L1 interactions to restore the immunological activity against cancer cells have been clinically validated. High-affinity mutants of the PD-1 ectodomain have recently been proposed as an alternative to antibodies to target PD-L1 on cancer cells, shedding new light on this research area. In this dynamic scenario, the PD-1 mutant, here reported, largely expands the chemical space of nonantibody and nonsmall-molecule inhibitor therapeutics that can be used to target cancer cells overexpressing PD-L1 receptors. The polyethylene glycol moieties and the immune response-stimulating carbohydrates, used as site-selective tags, represent the proof of concept for future applications.
Site-Selective Functionalized PD-1 Mutant for a Modular Immunological Activity against Cancer Cells / Fallarini S.; Cerofolini L.; Salobehaj M.; Rizzo D.; Gheorghita G.R.; Licciardi G.; Capialbi D.E.; Zullo V.; Sodini A.; Nativi C.; Fragai M.. - In: BIOMACROMOLECULES. - ISSN 1526-4602. - STAMPA. - 24:(2023), pp. 5428-5437. [10.1021/acs.biomac.3c00893]
Site-Selective Functionalized PD-1 Mutant for a Modular Immunological Activity against Cancer Cells
Cerofolini L.Investigation
;Salobehaj M.Investigation
;Gheorghita G. R.Investigation
;Licciardi G.Investigation
;Capialbi D. E.Investigation
;Sodini A.Investigation
;Nativi C.
Conceptualization
;Fragai M.
Conceptualization
2023
Abstract
Targeting immune checkpoints is a well-established strategy in cancer therapy, and antibodies blocking PD-1/PD-L1 interactions to restore the immunological activity against cancer cells have been clinically validated. High-affinity mutants of the PD-1 ectodomain have recently been proposed as an alternative to antibodies to target PD-L1 on cancer cells, shedding new light on this research area. In this dynamic scenario, the PD-1 mutant, here reported, largely expands the chemical space of nonantibody and nonsmall-molecule inhibitor therapeutics that can be used to target cancer cells overexpressing PD-L1 receptors. The polyethylene glycol moieties and the immune response-stimulating carbohydrates, used as site-selective tags, represent the proof of concept for future applications.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.