121 ICAM-1-specific affinity tuned CAR T cells expressing SSTR2 for real-time imaging

Background The use of CAR T cells for solid tumors has a number challenges, such as lack tumor-specific targets, cell exhaustion, and the immunosuppressive tumor microenvironment. To address these AffyImmune developed technologies to affinity tune track in patients. targeting moiety is tuned preferentially bind overexpressing target while leaving normal with low basal levels untouched, thereby increasing therapeutic window allowing more physiological killing. are designed express SSTR2 (somatostatin receptor 2), which allows tracking vivo via PET/CT scan using FDA-approved DOTATATE. Methods AIC100 was generated by tuning I-domain LFA-1, ligand ICAM-1. Various mutants 10 6 -fold difference were evaluated affinity. This allowed structure activity relationships be conducted expressing various against targets varying antigen densities. variant micromolar clearly most effective non-clinical animal models. currently being assess safety, expansion, localization, preliminary patients advanced thyroid cancer phase I study ( NCT04420754 ). Our uses modified toxicity probability interval design three dosage groups x , 100 500 cells. Results Preclinical studies demonstrated greater anti-tumor safety lower A single dose resulted elimination significantly improved survival animals. confirmed other high ICAM-1 models including breast, gastric, multiple myeloma. In Phase patient given 10-million cells, near synchronous imaging FDG DOTATATE revealed evidence transient expansion reduction at lesions, peak density coinciding spike numbers blood. Conclusions We have selectively spatiotemporally image Near-synchronous scans will enhance early detection off-tumor validation response. anticipate that our ‘tune track’ technology widely applicable developing potent yet safe hard-to-treat cancers. Trial Registration Ethics Approval IRB 19-12021154IACUC (animal welfare): All experiments performed accordance National Institute Health’s Guide Care Use Laboratory Animals. Animal handling protocols approved Institutional Committee Weill Cornell Medicine (Permit Number: 2012–0063).