Single VHH-directed BCMA CAR-T cells cause remission of relapsed/refractory multiple myeloma

Han, Lu; Zhang, Jishuai; Zhou, Jincheng; Zhou, Keshu; Xu, Bingying; Li, Linlin; Fang, Baijun; Yin, Qingsong; Zhu, Xuemei; Zhou, Hu; Wei, Xudong; Su, Hongchang; Zhang, Bing-Xiang; Wang, Yanan; Xiang, Bin; Gao, Quanli; Song, Yongping

doi:10.1038/s41375-021-01269-3

Cited by 28 publications

(35 citation statements)

References 15 publications

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“…Besides the molecular therapies (31), nanobodies are being used in the development of several cellular therapies (31)(32)(33)(34)(35). Developing nanobody therapies using traditional lab-based approaches still carries an overhead of many years of experimentation before they reach the clinic.…”

Section: Discussionmentioning

confidence: 99%

INDI – Integrated Nanobody Database for Immunoinformatics

Deszyński¹,

Młokosiewicz²,

Volanakis

et al. 2021

Preprint

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Nanobodies, a subclass of antibodies found in camelids, are a versatile molecular binding scaffold composed of a single polypeptide chain. The small size of nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first therapeutic approval in 2018 cementing the clinical viability of this format. Structured data and sequence information of nanobodies will enable the accelerated clinical development of nanobody-based therapeutics. Though the nanobody sequence and structure data are deposited in the public domain at an accelerating pace, the heterogeneity of sources and lack of standardization hampers reliable harvesting of nanobody information. We address this issue by creating the Integrated Database of Nanobodies for Immunoinformatics (INDI, http://research.naturalantibody.com/nanobodies). INDI collates nanobodies from all the major public outlets of biological sequences: patents, GenBank, next-generation sequencing repositories, structures and scientific publications. We equip INDI with powerful nanobody-specific sequence and text search facilitating access to more than 11 million nanobody sequences. INDI should facilitate development of novel nanobody-specific computational protocols helping to deliver on the therapeutic promise of this drug format.

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Section: Discussionmentioning

confidence: 99%

INDI – Integrated Nanobody Database for Immunoinformatics

Deszyński¹,

Młokosiewicz²,

Volanakis

et al. 2021

Preprint

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“…Most CARs developed and tested in clinical studies have utilized scFvs, usually derived from murine monoclonal antibodies [ 23 , 24 ]. Both humoral and cellular responses triggered by the murine-derived scFvs included in the CAR structure may lead to quick clearance of the CAR-T cells from circulation and thus increase the risk of relapse [ 25 , 26 ].…”

Section: Structural Elements Contribute To Car’s Potencymentioning

confidence: 99%

CAR-T cell potency: from structural elements to vector backbone components

Mazinani

Rahbarizadeh

2022

Biomark Res

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Chimeric antigen receptor (CAR) T cell therapy, in which a patient’s own T lymphocytes are engineered to recognize and kill cancer cells, has achieved remarkable success in some hematological malignancies in preclinical and clinical trials, resulting in six FDA-approved CAR-T products currently available in the market. Once equipped with a CAR construct, T cells act as living drugs and recognize and eliminate the target tumor cells in an MHC-independent manner. In this review, we first described all structural modular of CAR in detail, focusing on more recent findings. We then pointed out behind-the-scene elements contributing to CAR expression and reviewed how CAR expression can be drastically affected by the elements embedded in the viral vector backbone.

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“…These are composed of only two heavy chains, in which the target recognition module is composed of a single variable domain (VHH); they are smaller and more stable than conventional scFvs (26). Importantly, nanobodies can be easily humanized for therapeutic safety with comparable antigen-binding affinity and specificity to that of traditional scFvs (26)(27)(28)(29).…”

Section: Car-t Therapymentioning

confidence: 99%

CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies

Evtimov²,

Jenkin

et al. 2022

Front. Immunol.

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Chimeric antigen receptor (CAR)-T therapy has demonstrated remarkable outcomes for B cell malignancies, however, its application for T cell lymphoma, particularly cutaneous T cell lymphoma (CTCL), has been limited. Barriers to effective CAR-T cell therapy in treating CTCL include T cell aplasia in autologous transplants, CAR-T product contamination with leukemic T cells, CAR-T fratricide (when the target antigen is present on normal T cells), and tumor heterogeneity. To address these critical challenges, innovative CAR engineering by targeting multiple antigens to strike a balance between efficacy and safety of the therapy is necessary. In this review, we discuss the current obstacles to CAR-T cell therapy and highlight potential targets in treating CTCL. Looking forward, we propose strategies to develop more powerful dual CARs that are advancing towards the clinic in CTCL therapy.

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Single VHH-directed BCMA CAR-T cells cause remission of relapsed/refractory multiple myeloma

Cited by 28 publications

References 15 publications

INDI – Integrated Nanobody Database for Immunoinformatics

INDI – Integrated Nanobody Database for Immunoinformatics

CAR-T cell potency: from structural elements to vector backbone components

CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies

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