Adaptor CAR Platforms—Next Generation of T Cell-Based Cancer Immunotherapy

Arndt, Claudia; Faßlrinner, Frederick; Loureiro, Liliana R.; Koristka, Stefanie; Feldmann, Anja; Bachmann, Michael

doi:10.3390/cancers12051302

Cited by 51 publications

(83 citation statements)

References 108 publications

(258 reference statements)

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“…Furthermore, the 7B6 epitope is also cryptic and not accessible in native human La protein (see also Results). Both epitope sequences have been carefully characterized and confirmed in numerous studies by using them as peptide tags [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. For example, the 7B6 sequence was introduced in the sequence of the extracellular domain of chimeric antigen receptor (CAR) genes and used for estimation of the transduction rate of CAR T cells and their enrichment by Fluorescence-Activated Cell Sorting (FACS ) [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, the 7B6 sequence was introduced in the sequence of the extracellular domain of chimeric antigen receptor (CAR) genes and used for estimation of the transduction rate of CAR T cells and their enrichment by Fluorescence-Activated Cell Sorting (FACS ) [ 30 ]. Moreover, both modular CAR T cell platforms, UniCARs and RevCARs, are based on the 5B9 and 7B6 epitope/paratope combination [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

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T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Bachmann

Bartsch

Bippes

et al. 2021

IJMS

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Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens’ syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Bachmann

Bartsch

Bippes

et al. 2021

IJMS

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“…The adaptor CAR T cell field, in which antibodies, Fabs or other biologic constructs are used to link universal CARs to tumor antigens is an adjacent technology solution. Examples include CARs that target Fc receptors, peptides, haptens and leucine zipper binding [ 67 ]. The singular issue with such technologies is their reliance on tumor antigen expression, thus if the target antigen is lost the adaptor won’t bind and the CAR cannot recognize the tumor cell.…”

Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Ambrose¹,

Su²,

Wu³

et al. 2021

PLoS ONE

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Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2-positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack tumor antigens on any cancer.

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“…The first of these classes is the most developed and so we shall focus here on the corresponding clinical trials. For more information on the different categories of CAR, adaptor molecules, designs, side effects, and perspectives, see [ 69 ].…”

Section: From Conventional Car-t Cells To Next-generation Car-t Cementioning

confidence: 99%

“…The second trial has not started yet but will investigate the activity of a combination of α-PNE CAR-T cells (CLBR001) and a CD19 Fab switch (SWI019) in patients with relapsed/refractory B cell cancers [ 86 ]. Furthermore, α-FITC CARs with EC17 (folate-FITC) are advancing towards clinical development in an indication of osteosarcoma [ 69 ].…”

Section: From Conventional Car-t Cells To Next-generation Car-t Cementioning

confidence: 99%

Engineering Next-Generation CAR-T Cells for Better Toxicity Management

Andrea

Chiron

Bessoles

et al. 2020

IJMS

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Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy—notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding various components (such as OFF- and ON-switch CARs) or by combining multi-antigen-targeting OR-, AND- and NOT-gate CAR-T cells. This research has laid the foundations for a whole new generation of therapeutic CAR-T cells. Here, we review the most promising CAR-T cell safety strategies and the corresponding preclinical and clinical studies.

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Adaptor CAR Platforms—Next Generation of T Cell-Based Cancer Immunotherapy

Cited by 51 publications

References 108 publications

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Engineering Next-Generation CAR-T Cells for Better Toxicity Management

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