Development of Monoclonal Antibodies in China: Overview and Prospects

Zhang, Maoyu; Lu, Jin‐Jian; Wang, Liang; Gao, Zi-Chao; Hu, Hao; Ung, Carolina Oi Lam; Wang, Yitao

doi:10.1155/2015/168935

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…Patents with the largest out-degree (i.e., humanized mAbs) clearly dominate therapeutic mAb R&D. It has been noted that fully human mAbs have gradually become the hottest topic in the field since the 2000s. 29,30,48,49 This pattern has not as yet been explained by reference to the citation network. By comparison with humanized mAbs, fully human mAbs form less complicated patent citation relationships, probably because patents usually follow long after R&D activities.…”

Section: Downloaded By [Uq Library] At 22:10 27 July 2015mentioning

confidence: 92%

Research and development of therapeutic mAbs: An analysis based on pipeline projects

Geng

Kong

et al. 2015

Human Vaccines & Immunotherapeutics

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As the subject of active research and development (R&D) in recent decades, monoclonal antibodies have emerged among the major classes of therapeutic agents for treatment of many human diseases, especially cancers, infections, and immunological disorders. This article surveys the landscape of R&D projects of therapeutic monoclonal antibodies (mAbs), which are mostly used for disease immunotherapy, from a number of perspectives, including therapeutic indications, development phases, participants, and citation of related patents. The results of this research can be used as a reference resource for pharmaceutical researchers, investors, and policymakers in the field of therapeutic mAbs.

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Section: Downloaded By [Uq Library] At 22:10 27 July 2015mentioning

confidence: 92%

Research and development of therapeutic mAbs: An analysis based on pipeline projects

Geng

Kong

et al. 2015

Human Vaccines & Immunotherapeutics

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“…However, progress has often been described as slow (101, 114), and only two small molecules (a CCR5 antagonist Maraviroc (31) and a CXCR4 antagonist Plerixafor (26)) against the chemokine receptor system are currently approved for use. Additionally, two antibody-based drugs, an anti-CCR4 monoclonal antibody Mogamulizumab (33) and an anti-CXCL8 antibody Abcream (145), are approved in Japan and China, respectively.…”

Section: Introductionmentioning

confidence: 99%

What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

Kufareva

Gustavsson

Zheng

et al. 2017

Annu. Rev. Biophys.

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Chemokines and their cell surface G protein-coupled receptors are critical for cell migration not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provide unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal complicated and diverse structural foundations of small molecule antagonism and allostery, highlight inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novel epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.

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“…Design and Generation of Y111 based on patented Y-body® platform Y111 (PD-L1 x CD3), aCD3-targeting bispeci c antibody, that redirected T cells to attack PD-L1-expressing cancer cells, was designed with the Y-body® format in structure [25,28]. Y111 consisted of a Fab structure targeting PD-L1 derived from Tecentriq (Atezolizumab), a single chain variable fragment (scFv) for activating CD3 originated from a monoclonal antibody 2A5 (WO2020168555), and a modi ed Fc region (Fig.…”

Section: Resultsmentioning

confidence: 99%

Bi-specific Antibody Y111, Targeting PD-L1 and CD3 Considerably Enhances the Therapeutic Efficacy of Adoptive Transferred Vγ2Vδ2 T Cells

Yang¹,

Shen²,

Gong³

et al. 2020

Preprint

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Background: Anti-cancer immunotherapy based on the adoptive transfer of Vγ2Vδ2 T cells has benefited to some patients in clinical trials, but the overall responses are inconsistent. Therefore, new strategies are urgently needed to improve the current therapy.Methods: In this study, a designed bispecific antibody Y111, which binds to both CD3 and PD-L1, is applied to optimally potentiate Vγ2Vδ2 T cell-based killing of cancer cells. The binding activities of Y111 was determined by Flow cytometry. CFSE/PI-based flow cytometry was applied to check the re-directed killing ability induced by Y111 in the condition of using T cell subsets, or expanded- and purified- Vγ2Vδ2 T cells as effector cells. Moreover, expanded- and purified- Vγ2Vδ2 T cells were co-cultured with tumor cells in the presence/absence of Y111 to assess the activation, degranulation, and cytokine production by intracellular cytokine staining, and CBA method. Finally, NPG-based subcutaneous tumor mouse models were used to check the in vivo therapeutic efficacy of the combination of transfused Vγ2Vδ2 T cells and Y111.Results: Due to its binding activities, Y111 apparently prompts fresh αβ-mediated lysis of tumor cell line H358 cells, but spare the effect on the fresh enriched Vγ2Vδ2 T cells from the same donors. However, Y111 increases cytotoxicity of expanded and purified Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines in a tumor cell dependent fashion. Y111 also prompted the releases of granzyme B, IFNγ and TNFα. Supporting to these observations in vitro, a combination of adoptive transferring Vγ2Vδ2 T cell and Y111 into the tumor-bearing NPG mice inhibited the growth of the established tumors in the mice.Conclusions: Taken together, our data suggest clinical potential for adoptive transferring the bispecific antibody-armored Vγ2Vδ2 T cells to treat solid tumors, such as NSCLC.

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Development of Monoclonal Antibodies in China: Overview and Prospects

Cited by 10 publications

References 38 publications

Research and development of therapeutic mAbs: An analysis based on pipeline projects

Research and development of therapeutic mAbs: An analysis based on pipeline projects

What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

Bi-specific Antibody Y111, Targeting PD-L1 and CD3 Considerably Enhances the Therapeutic Efficacy of Adoptive Transferred Vγ2Vδ2 T Cells

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