B7-H3 Chimeric Antigen Receptor Redirected T Cells Target Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma

Zi, Zhenguo; Zhao, Haihong; Wang, Huanyu; Ma, Xiaojing; Wei, Fang

doi:10.3390/cancers12123815

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…Several B7-H3 targeted antibodies have entered into phase I/II clinical trials against multiple solid tumor types, such as enoblituzumab, an Fc-engineered antibody developed by MacroGenics, as well as antibody conjugated drug MGC018 and DS-7300a developed by MacroGenics and Daiichi Sankyo. The antitumor effects of B7-H3 targeted CAR-T cells have also been frequently reported both in preclinical and in clinical trials for glioma ( 33 ), anaplastic meningioma ( 34 ), pediatric brain tumors ( 35 ), as well as lymphoma ( 36 ). We also observed significant antitumor effects when co-cultured chordoma tumor spheres with B7-H3-targeted CAR-T cells.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

Cheng

Zhang

et al. 2021

Front. Oncol.

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Objectivechordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.Methodswe profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.ResultsWe found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.ConclusionsOur results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.

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Section: Discussionmentioning

confidence: 99%

B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

Cheng

Zhang

et al. 2021

Front. Oncol.

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“…It has obvious proliferative activity and memory phenotype after receiving B7-H3 stimulation. Under the premise of strict control of CRS, B7-H3 CAR-T is expected to become another important therapeutic target for ALK+ ALCL after ALK and CD30 ( 150 ).…”

Section: Strategies To Overcome Alk Tki Resistancementioning

confidence: 99%

Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma

Wang

et al. 2022

Front. Oncol.

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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed at early stages of normal development and in various cancers including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), in which it is the main therapeutic target. ALK tyrosine kinase inhibitors (ALK TKIs) have greatly improved the prognosis of ALK+ALCL patients, but the emergence of drug resistance is inevitable and limits the applicability of these drugs. Although various mechanisms of resistance have been elucidated, the problem persists and there have been relatively few relevant clinical studies. This review describes research progress on ALK+ ALCL including the application and development of new therapies, especially in relation to drug resistance. We also propose potential treatment strategies based on current knowledge to inform the design of future clinical trials.

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“…A B7-H3-redirected CAR based on scFvs from mAb 376.96 demonstrated strong cytotoxicity and cytokine production against target anaplastic large cell lymphoma cells in vitro and promptly eradicated tumor cells in mouse xenografts. In addition, B7-H3 CAR-T cells show growth capacity and a memory phenotype after stimulation using repeated antigen (63). A bispecific antibody targeting B7-H3 and 4-1BB (B7-H3×4-1BB) has been developed.…”

Section: B7-h3mentioning

confidence: 99%

B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?

et al. 2021

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T cells play a vital role in the immune responses against tumors. Costimulatory or coinhibitory molecules regulate T cell activation. Immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have shown remarkable benefits in patients with various tumor, but few patients have displayed significant immune responses against tumors after PD-1/PD-L1 immunotherapy and many have been completely unresponsive. Thus, researchers must explore novel immune checkpoints that trigger durable antitumor responses and improve clinical outcomes. In this regard, other B7 family checkpoint molecules have been identified, namely PD-L2, B7-H2, B7-H3, B7-H4 and B7-H6. The aim of the present article was to address the expression, clinical significance and roles of B7 family molecules in lymphoma, as well as in T and NK cell-mediated tumor immunity. B7 family checkpoints may offer novel and immunotherapeutic strategies for patients with lymphoma.

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B7-H3 Chimeric Antigen Receptor Redirected T Cells Target Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma

Cited by 12 publications

References 32 publications

B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma

B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?

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