B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells

Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer

“…The clinical benefits of this approach have been validated using CAR-CD19 T cells to treat a range of CD19 + hematological malignancies including B cell chronic lymphocytic leukemia (B-CLL) and acute lymphoblastic leukemia (ALL). [29][30][31][32] For example, Grupp and colleagues 30 recently reported a complete remission rate of 92% in pediatric patients with relapsed/refractory CD19 + ALL, while Davila et al 3 achieved an overall complete remission rate of 88% in adults with B-ALL. In many cases, clinical benefit correlated with the ability of infused cells to expand and persist in vivo.…”

The Flipside of the Power of Engineered T Cells: Observed and Potential Toxicities of Genetically Modified T Cells as Therapy

“…The severity of CRS does not appear to correlate with overall disease response, but most responding patients demonstrate some degree of CRS. [3][4][5][6][7] In patients with acute lymphoblastic leukemia (ALL), CRS has been correlated with disease burden at the time of infusion, and experience has demonstrated that more potent conditioning regimens may increase the likelihood of severe CRS and/or CAR-related toxicity. 8 Patients with severe CRS can also develop a macrophage activation syndrome (MAS) reminiscent of hemophagocytic lymphohistiocytosis, as demonstrated by overlapping cytokine profiles, hyperferritinemia, and evidence of hemophagocytosis on bone marrow biopsy.…”

Re-defining response and treatment effects for neuro-oncology immunotherapy clinical trials

“…Adoptive T cell therapies, particularly the use of chimeric antigen receptor (CAR) T cells, have generated unprecedented durable remissions in patients with refractory leukemia [9][10][11][12][13]. Strategies to engineer autologous T cells to express chimeric antibodies against tumor antigens have been in development for over 20 years, but have been limited by inadequate expansion and persistence of engineered T cells.…”