Humanization of Murine Monoclonal anti-hTNF Antibody: The F10 Story

Efimov, Grigory A.; Raats, Jos; Chirivi, Renato G. S.; Rosmalen, Jos W.G. van; Nedospasov, Sergei A.

doi:10.1134/s0026893317060061

Cited by 1 publication

(1 citation statement)

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“…After the final round of biopanning, individual phage clones displaying Fab were generated from colonies grown on output plates and tested for reactivity to rhMSLN by using the phage enzyme immunoassay, as previously described [24]. The selected mouse anti-human MSLN antibody was humanized by CDR-grafting methods, based on a previous study [25]. After searching for VH and VL framework sequences in the ImMunoGeneTics database of human germline sequences, IGHV1-3*01 and IGKV1-12*01 were selected as framework templates.…”

Section: Construction Of the Antibody Library And Selection Of Antibomentioning

confidence: 99%

A Novel T Cell-Engaging Bispecific Antibody for Treating Mesothelin-Positive Solid Tumors

Yoon¹,

Lee²,

Lee³

et al. 2020

Biomolecules

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As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors.

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Section: Construction Of the Antibody Library And Selection Of Antibomentioning

confidence: 99%