This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19)

Start Date11 Sep 2020

Sponsor / Collaborator

The University of California, San Francisco

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100 Clinical Results associated with anti-CD19 CAR-T cells(University of California)

100 Translational Medicine associated with anti-CD19 CAR-T cells(University of California)

100 Patents (Medical) associated with anti-CD19 CAR-T cells(University of California)

Literatures (Medical) associated with anti-CD19 CAR-T cells(University of California)

01 Dec 2024·Computational and Structural Biotechnology Journal

In silico and in vivo analysis reveal impact of c-Myc tag in FMC63 scFv-CD19 protein interface and CAR-T cell efficacy

Article

Author: Lourenzoni, Marcos Roberto ; Batista-Silva, Leonardo Ribeiro ; Abdo, Luiza ; Correia, Eduardo Mannarino ; Aragão, Emmanuel Arthur Albuquerque ; Bonamino, Martín Hernán ; Lima, Ana Julia Ferreira ; de Oliveira Andrade, Clara ; Hajdu, Karina Lobo

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

01 Nov 2024·Rheumatology

Comment on: Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies

Article

Author: Schneider, Udo ; Krusche, Martin ; Stenzel, Werner ; Ruffer, Nikolas

01 Aug 2024·Journal of Zhejiang University-SCIENCE B

Waldenström macroglobulinemia: a challenging case treated with anti-CD19 CAR-T cell therapy

Article

Author: Yang, Yang ; He, Jingsong ; Cai, Zhen ; Hu, Yongxian ; Gu, Xiaolin

Waldenström macroglobulinemia (WM) is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M (IgM) protein (Owen et al., 2003). Common signs and symptoms include fatigue due to anemia, lymph node enlargement, hepatosplenomegaly, thrombocytopenia, symptoms related to high viscosity, and peripheral neuropathy, among others. Despite significant advances in WM treatment, this type of indolent lymphoma remains incurable, with a wide array of patient outcomes (Ruan et al., 2020). In recent years, chimeric antigen receptor T (CAR-T) cell therapy targeting cluster of differentiation 19 (CD19) has shown unprecedented response rates and durability in the treatment of B-cell malignancies. In this report, we describe a challenging case of WM that involved multiple extramedullary sites, relapsed, and was refractory to chemotherapy, immunotherapy, and targeted therapy. After anti-CD19 CAR-T cell therapy, the tumor burden significantly decreased and the patient's condition remained stable at the writing of this report.

100 Deals associated with anti-CD19 CAR-T cells(University of California)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Hodgkin Lymphoma	Phase 1	US	The V Foundation	30 Oct 2024
Burkitt Lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Follicular Lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Lymphoplasmacytic Lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Mantle-Cell Lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Mediastinal large B-cell lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Non-Hodgkin's lymphoma refractory	Phase 1	US	The University of California, San Francisco	11 Sep 2020
Small Lymphocytic Lymphoma	Phase 1	US	The University of California, San Francisco	11 Sep 2020

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anti-CD19 CAR-T cells(University of California)

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