Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study
Iyer S, Sica R, Ho P, Prica A, Zain J, Foss F, Hu B, Beitinjaneh A, Weng W, Kim Y, Khodadoust M, Huen A, Williams L, Ma A, Huang E, Ganpule A, Nagar S, Sripakdeevong P, Cullingford E, Karnik S, Dequeant M, Patel J, He X, Li Z, He Q, Mendonez J, Keegan A, Horwitz S. Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. The Lancet Oncology 2024 PMID: 39617017, DOI: 10.1016/s1470-2045(24)00508-4.Peer-Reviewed Original ResearchT-cell lymphomaPeripheral T-cell lymphomaCutaneous T-cell lymphomaRefractory T-cell lymphomaEastern Cooperative Oncology GroupChimeric antigen receptorCytokine release syndromeCAR+ T cellsSerious adverse eventsAdverse eventsT cellsOpen-labelRefractory peripheral T-cell lymphomaAllogeneic chimeric antigen receptorHealthy donor T cellsRefractory T-cell malignanciesCAR-T cell therapyMedian patient follow-upIncidence of adverse eventsDonor T cellsObjective response rateSystemic therapy linesDose-limiting toxicityT-cell therapyDose-escalation studyGeneration and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy
Ren J, Liao X, Lewis J, Chang J, Qu R, Carlson K, Foss F, Girardi M. Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy. Nature Communications 2024, 15: 519. PMID: 38225288, PMCID: PMC10789731, DOI: 10.1038/s41467-024-44786-2.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityDonor T cellsT cellsAdeno-associated virus transductionHealthy donor T cellsHost-versus-graft reactivityEnhanced antibody-dependent cellular cytotoxicityCAR-T cellsGraft-versus-hostT cell killingT-cell malignanciesMalignant T cellsNormal T-cellT cell receptorOff-target toxicityPre-existing immunoreactivityCAR-TDisease relapseCellular cytotoxicityVirus transductionCurrent treatmentPersister killingFc engineeringB2MIn vivo