CD22-CAR T Cells Induce Remissions in CD19-CAR Naïve and Resistant B-ALL

By T. Fry, N. Shah, R. Orentas, M. Stetler-Stevenson, C. Yuan, S. Ramakrishna, P. Wolters, Staci Martin, Cindy P. Delbrook, B. Yates and 14 more. Nature Medicine, 2017

1,111 citations recorded by the source corpus.

Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre–B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving ≥1 × 106 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19dim or CD19− B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22+ cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function.

Subfields: Electrical and Electronic Engineering, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/a593629f5ac0daf0aca60ae0a7b526721ba29319

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Citations in the corpus

• Clinical and Biologic Correlates of Neurotoxicity Associated with CAR T Cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia (B-ALL) (2018, result): “Although other studies have additionally shown an association between severe neurotoxicity and higher infused cell dose (5, 22), we did not observe such an association.”
• ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells (2018, background): “CAR therapies targeting CD22 in B cell malignancies [5] and B cell maturation antigen (BCMA) in multiple myeloma [6] have been highly successful in early trials and are also forthcoming, along with combination approaches targetingmultiple antigens simultaneously.”
• Tumor Antigen Escape from CAR T-cell Therapy. (2018, background): “In recognizing that single antigen targeting was unlikely to be successful in many cases of pediatric B-ALL, we developed a CAR targeting CD22, another B-cell antigen broadly expressed on lymphoblasts (63).”