Nanobody-based CAR T cells targeting intracellular tumor antigens

Li, Haixia; Zhong, Dani; Luo, Huiguan; Shi, Wei; Xie, Shenxia; Qiang, Hangbiao; Zhu, Linghua; Lin, Guangyong; Li, Jun; Sun, Shuyang; Ding, Ziqiang; Yang, Xiaomei; Lü, Xiaoling

doi:10.1016/j.biopha.2022.113919

Cited by 12 publications

(19 citation statements)

References 79 publications

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“…The scFv format permits facile reformatting of antibodies derived from conventional immunization campaigns. These are almost entirely, to date, raised against the extracellular domains of cell-surface proteins that are identified as viable tumor targets, though there are recent developments in generating scFvs that recognize intracellular tumor antigens with limited MHC restriction (which is a limiting factor in TCR-T cell therapy) through display technologies [ 37 , 38 ] or using structural analysis to drive rationale engineering to optimize the binder [ 39 , 40 ]. It remains to be seen how broadly applicable and indeed successful this approach will be.…”

Section: Choice Of Scaffoldmentioning

confidence: 99%

Bringing cell therapy to tumors: considerations for optimal CAR binder design

Smith

2023

Antibody Therapeutics

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Chimeric antigen receptor (CAR)-T cells have revolutionized the immunotherapy of B-cell malignancies and are poised to expand the range of their impact across a broad range of oncology and non-oncology indications. Critical to the success of a given CAR is the choice of binding domain, as this is the key driver for specificity and plays an important role (along with the rest of the CAR structure) in determining efficacy, potency and durability of the cell therapy. While antibodies have proven to be effective sources of CAR binding domains, it has become apparent that the desired attributes for a CAR binding domain do differ from those of a recombinant antibody. This review will address key factors that need to be considered in choosing the optimal binding domain for a given CAR and how binder properties influence and are influenced by the rest of the CAR.

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Section: Choice Of Scaffoldmentioning

confidence: 99%

Bringing cell therapy to tumors: considerations for optimal CAR binder design

Smith

2023

Antibody Therapeutics

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“…CARs were first developed in T cells with four distinct functional domains: an extracellular antigen-recognition domain, a flexible hinge region, a transmembrane domain, and an intracellular T cell signaling domain ( 23 ). The extracellular antigen-binding domain could be comprised of various structures including single chain variable fragments of antibodies (scFv) ( 24 ), cell receptors ( 25 ), ligands ( 26 ), other derived peptides programmed for specific interactions ( 27 ), or nanobodies ( 28 ). This domain is constructed with a range of specificities to the specified target to provide ample stimulation while avoiding activation-induced cell death ( 23 ).…”

Section: Engineering Strategies To Enhance Antitumor Efficacymentioning

confidence: 99%

Genetic engineering strategies to enhance antitumor reactivity and reduce alloreactivity for allogeneic cell-based cancer therapy

et al. 2023

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The realm of cell-based immunotherapy holds untapped potential for the development of next-generation cancer treatment through genetic engineering of chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapies for targeted eradication of cancerous malignancies. Such allogeneic “off-the-shelf” cell products can be advantageously manufactured in large quantities, stored for extended periods, and easily distributed to treat an exponential number of cancer patients. At current, patient risk of graft-versus-host disease (GvHD) and host-versus-graft (HvG) allorejection severely restrict the development of allogeneic CAR-T cell products. To address these limitations, a variety of genetic engineering strategies have been implemented to enhance antitumor efficacy, reduce GvHD and HvG onset, and improve the overall safety profile of T-cell based immunotherapies. In this review, we summarize these genetic engineering strategies and discuss the challenges and prospects these approaches provide to expedite progression of translational and clinical studies for adoption of a universal cell-based cancer immunotherapy.

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“…20 Various preclinical and clinical studies are also being conducted to investigate GPC3-targeted therapies either as a single agent or along with therapeutic agents such as GPC3-targeted bispecific trifunctional antibodies (trAbs), GPC3 peptide vaccine and GPC3 CAR-T therapy. 21 However, these studies are still at the stage of clinical trials and have not yet been applied in the clinic. Therefore, the measurement of peripheral blood GPC3 concentrations in tumor patients before and after immunotherapy is essential to assess the suitability of anti-GPC3 antibody therapy for the patient.…”

Section: Introductionmentioning

confidence: 99%