ADDENDUM: T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells

Zah, Eugenia; Lin, Meng-Yin; Silva-Benedict, Anne; Jensen, Michael C.; Chen, Yvonne Y.

doi:10.1158/2326-6066.cir-16-0108

Cited by 21 publications

(18 citation statements)

References 4 publications

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“…Additionally, engineering CAR T cells to express more than one CAR may lessen the ability of tumor cells to downregulate surface proteins targeted by monospecific CAR therapies. The development of bispecific CAR T cells, such as those that recognize both CD19 and CD20, another generally B-cell-specific surface antigen, may increase response rates and improve durability of responses by preventing antigen-loss tumor escape mechanisms [66,67].…”

Section: Discussionmentioning

confidence: 99%

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

Roberts

Better

Bot

et al. 2017

Leukemia & Lymphoma

103

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Section: Discussionmentioning

confidence: 99%

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

Roberts

Better

Bot

et al. 2017

Leukemia & Lymphoma

103

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“…Another study used bispecific CARs that targeted both CD19 and CD20 in order to minimize antigen escape from CD19-negative leukemia. Those bispecific CAR T cells were able to eradicate heterogeneous populations of leukemic cells in NSG mice (37).…”

Section: Cancer and Hiv: Shared Challenges And Opportunitiesmentioning

confidence: 99%

CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV

Kim

Hege²,

Riley

2019

Front. Immunol.

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Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expressing T cells as part of a strategy to cure HIV. Many lessons have been learned on how to best engineer T cells to cure cancer, but not all of these lessons apply when developing CARs to treat and cure HIV. This mini review will focus on how early CAR T cell studies in HIV paved the way for cancer CAR T cell therapy and how progress in cancer CAR therapy has and will continue to be instructive for the development of HIV CAR T cell therapy. Additionally, the unique challenges that must be overcome to develop a successful HIV CAR T cell therapy will be highlighted.

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“…One of the approaches to achieve dual targeting is the use of tandem CARs. Different tandem CARs have already been reported [8,[23][24][25]. However, the generation of tandem CARs can be challenging due to potential cross pairing between the V H and V L of the different scFvs [26].…”

Section: Introductionmentioning

confidence: 99%

Rapid and Effective Generation of Nanobody Based CARs using PCR and Gibson Assembly

Munter

Parys

Bral

et al. 2020

IJMS

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Recent approval of chimeric antigen receptor (CAR) T cell therapy by the European Medicines Agency (EMA)/Federal and Drug Administration (FDA) and the remarkable results of CAR T clinical trials illustrate the curative potential of this therapy. While CARs against a multitude of different antigens are being developed and tested (pre)clinically, there is still a need for optimization. The use of single-chain variable fragments (scFvs) as targeting moieties hampers the quick generation of functional CARs and could potentially limit the efficacy. Instead, nanobodies may largely circumvent these difficulties. We used an available nanobody library generated after immunization of llamas against Cluster of Differentiation (CD) 20 through DNA vaccination or against the ectodomain of CD33 using soluble protein. The nanobody specific sequences were amplified by PCR and cloned by Gibson Assembly into a retroviral vector containing two different second-generation CAR constructs. After transduction in T cells, we observed high cell membrane nanoCAR expression in all cases. Following stimulation of nanoCAR-expressing T cells with antigen-positive cell lines, robust T cell activation, cytokine production and tumor cell lysis both in vitro and in vivo was observed. The use of nanobody technology in combination with PCR and Gibson Assembly allows for the rapid and effective generation of compact CARs.

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ADDENDUM: T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells

Cited by 21 publications

References 4 publications

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV

Rapid and Effective Generation of Nanobody Based CARs using PCR and Gibson Assembly

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