Blinatumomab, a CD19/CD3-bispecific T-cell engager (BiTE) immuno-oncology therapy for the treatment of B-cell malignancies, is associated with neurologic adverse events in a subgroup of patients.
Recently, the single-cell metric termed polyfunctional strength index (PSI™) by IsoCode chip computed from preinfusion anti-CD19 chimeric antigen receptor (CAR)-T cell products has demonstrated a significant association with clinical response and cytokine release syndrome (CRS) of cancer patient to the therapy after cell product infusion.
CD19-targeted chimeric antigen receptor-modified T cell (CAR-T cell) therapy has shown excellent antitumor activity in patients with relapsed/refractory B cell malignancies, with very encouraging response rates and outcomes.
CD19-targeted chimeric antigen receptor (CAR) modified T cell immunotherapy is a novel treatment with promising results in patients with relapsed/refractory lymphoid malignancies.
Treatment with chimeric antigen receptor (CAR)-modified T cells targeting CD19 has proved successful in patients with relapsed/refractory B cell malignancies.
Lymphocyte collection at our center was well tolerated and 100% successful in manufacturing CD19-directed CAR T cells from adult patients with B-cell malignancies despite low CE in some patients.
Chimeric antigen receptors against CD19 (anti-CD19-CAR) are widely recognized and used by not only researchers associated with immunology, molecular biology, and cell biology but also physicians to treat B-cell malignancies.
The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy that involves reprogramming the patient's own T cells to identify and eliminate CD19-expressing cells.
The unprecedented efficacy of CD19-CAR T cells against B-cell malignancies has inspired oncologists to extend these efforts for the treatment of solid tumors.
Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs).
<b>Background:</b> CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies.
In 2017, the Food and Drug Administration approved two CD19-targeted CAR T-cell therapies (Kymriah™, Novartis, and Yescarta™, Kite Pharma/Gilead Sciences) that have remarkable efficacy in some B-cell malignancies.
T cells expressing anti-CD19 chimeric antigen receptors (CARs) demonstrate impressive efficacy in the treatment of systemic B cell malignancies, including B cell lymphoma.
Most felt that a history of malignancy (57%), prior allo-HCT for B-NHL (78%-81%) and prior treatment with anti-CD19/CD3 BiTE antibodies (76%-86%) do not constitute contra-indications to CAR T therapy.
Today, CAR T-cell therapy has proven successful in the treatment of haematological malignancies and the first CD19 CAR T-cell products has already entered the market.
Blinatumomab (Blincyto, Amgen), a bi-specific antibody, is a first-in-class, targeted immunotherapy agent for treatment of B-cell malignancies with a novel mechanism of action which involves in-vivo engagement of the patient's T cells with CD19-expressing tumour cells.
In this review we describe CRS and neurotoxicity in patients with B cell malignancies treated with CD19 CAR-T cells in pivotal trials, and also provide insight into potential mechanisms associated with these toxicities based on studies conducted in a phase 1/2 clinical trial at the Fred Hutchinson Cancer Research Center.
Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and potent effects in CD19+ B-cell malignancies.
Although remarkable results have been attained by adoptively transferring T cells expressing fully murine and/or humanized anti-CD19 chimeric antigen receptors (CARs) to treat B cell malignancies, evidence of human anti-mouse immune responses against CARs provides a rationale for the development of less immunogenic CARs.
To date, CD19-targeted chimeric antigen receptor T (CAR T) cells have been the most extensively studied, showing complete and durable responses in B-cell malignancies.
Denintuzumab mafodotin (SGN-CD19A) is a CD19-targeting antibody-drug conjugate, comprising a monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin F. Since denintuzumab mafodotin has previously shown activity against B-cell malignancies in early-stage clinical trials, it was of interest to test it against the Pediatric Preclinical Testing Program preclinical models of CD19<sup>+</sup> pediatric acute lymphoblastic leukemia (ALL).