2024
AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of response
2022
The current state of the art and future trends in RAS-targeted cancer therapies
Punekar S, Velcheti V, Neel B, Wong K. The current state of the art and future trends in RAS-targeted cancer therapies. Nature Reviews Clinical Oncology 2022, 19: 637-655. PMID: 36028717, PMCID: PMC9412785, DOI: 10.1038/s41571-022-00671-9.Peer-Reviewed Original ResearchConceptsDuration of responseNovel combination therapiesCombination therapyClinical trialsTherapeutic strategiesSolid tumorsMutant KRASTumor microenvironmentDrug resistanceRAS pathwayCancer cellsDevelopment of inhibitorsCancer therapyOncogenic RASPatientsOncogenic proteinsTherapyKRASResistance mechanismsMutant isoformsInhibitorsRASMalignancyTumorsCancer