Humanization of Chimeric Anti-CD20 Antibody by Logical and Bioinformatics Approach with Retention of Biological Activity

Khoo, Yoke L; Cheah, Swee Hung; Chong, Heilly

doi:10.2217/imt-2017-0016

Cited by 5 publications

(7 citation statements)

References 41 publications

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“…Eight studies were excluded as they were not focused in the field of IMIDs. Finally, 7 studies were included in our systematic review [15][16][17][18][19][20][21]. Most studies were in vitro studies (6 [86%]) [15][16][17][18][19][20] followed by a phase I clinical trial (14%) [21] (Tables 1).…”

Section: Systematic Reviewmentioning

confidence: 99%

Biobetters in patients with immune-mediated inflammatory disorders: An international Delphi consensus

D’Amico

Solitano

Aletaha

et al. 2021

Autoimmunity Reviews

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Section: Systematic Reviewmentioning

confidence: 99%

Biobetters in patients with immune-mediated inflammatory disorders: An international Delphi consensus

D’Amico

Solitano

Aletaha

et al. 2021

Autoimmunity Reviews

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“…Affinity constant for the produced chimeric antibody calculated against the recombinant form of p19 resulted in 10 -5 M, though low, is in accordance with values expected for antibodies of subclass M, as is the monoclonal parental antibody. Having corroborated the specificity of the new antibody it could be of potential use in therapeutics, the necessary improvement of affinity could be performed by bioinformatic analysis of the sequence and subsequent modification [10]. Figure 1.…”

Section: Discussionmentioning

confidence: 98%

“…Chimeric antibodies keep the parent murine variable regions consequently the binding specificity and affinity. Though preserve more mouse sequence than other methods, they have the advantage of easier to construct and can be easily in vitro reshaped [10]. In this work we successfully generate a chimeric antibody that recognizes the p19 subunit of the interleukin IL-23 after immunization of mice with a synthetic peptide derived from the protein sequence, as immunogenic epitope.…”

Section: Introductionmentioning

confidence: 99%

Generation of a Chimeric Antibody against a Synthetic Peptide Derived From IL-23p19 with Potential Therapeutic Application

Pérez-Etcheverry

Carmen

2017

IRA-JAS

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Aim: To construct an express a mouse-human chimeric antibody against IL-23p19 using a synthetic peptide as immunogen.Methods: Immunization of mice with a synthetic peptide derived from the IL-23p19 sequence and generation of hybridoma secreting specific antibodies. The chimeric antibody was created using two eukaryotic plasmid constructions; one of them carrying the light mouse-human chain and the other the heavy mouse-human chain. CHO-K1 cells were cotransfected with both plasmids and stable transfectants were grown in selective culture medium.Results: A chimeric version of anti-IL-23p19 was successfully constructed and expressed in eukaryotic cells. The expressed chimeric antibody showed specific recognition not only of the peptide used as immunogen but also the subunit p19 and the complete interleukin Il-23.Conclusion: A Chimeric antibody that was developed against a synthetic peptide, which is able to recognize the parent protein IL23 biologically active, could be developed into a targeted therapy in diseases with chronic inflammation.

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“…Mouse antibody is recognized as a foreign antigen in human and can be rejected by human immune system, which can result in rapid mouse antibody clearance, low anti-tumor efficacy or hypersensitivity reactions in human body [12]. As the development of genetic engineering, humanized antibody or chimeric antibody were developed to reduce the antigenicity of mouse antibody [13]. Even though immunogenicity of the mouse antibody may be reduced, it cannot be completely eliminated.…”

Section: Discussionmentioning

confidence: 99%

“…Mouse-derived mAbs can result in rapid antibody clearance, loss of efficacy or hypersensitivity reactions in cancer patients [12]. Along with the development of genetic engineering, chimeric antibodies or humanized antibodies were developed and reduced only some of their antigenicity [13]. MAbs are difficult to penetrate into solid tumors due to their large molecular weight and expensive to be manufactured with mammalian cells [14,15].…”

Section: Introductionmentioning

confidence: 99%

Novel single-domain antibodies against the EGFR domain III epitope exhibit the anti-tumor effect

Chen

Hong

et al. 2020

J Transl Med

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Background Monoclonal antibodies (mAbs) have been used for cancer therapy. They are large and have some disadvantages limiting their use. Smaller antibody fragments are needed as their alternatives. A fully human single-domain antibody (sdAb) has a small size of only 15 kDa and consists of only the variable domain of the human antibody heavy chain (VH). It has no immunogenicity. It can easily penetrate into tumor tissues, target an epitope inaccessible to mAb and be manufactured in bacteria for a low cost. Epidermal growth factor receptor (EGFR) is over-expressed in many cancer cells and is a good target for cancer therapy. Methods The EGFR protein fragment located on the EGFR extracellular domain III was chosen to screen a human sdAb library. Five human anti-EGFR sdAbs were identified. Their specific binding to EGFR was confirmed by ELISA, Western blotting and flow cytometry. Their anti-tumor effects were tested. Results Five novel fully human anti-EGFR sdAbs were isolated. They specifically bound to EGFR, not to the seven unrelated proteins as negative controls. They also bound to the three different human cancer cell lines, but not to the two cell lines as negative controls. They inhibited cell proliferation, migration and invasion and increased apoptosis of these three cancer cell lines. Two of them were tested for their anti-tumor effect in vivo and showed the anti-tumor activity in a mouse xenograft model for human lung cancer. Immunohistochemical staining of xenograft tumors also showed that their anti-tumor effects were associated with the inhibition of cancer cell proliferation and the promotion of cancer cell apoptosis. Conclusions This study clearly demonstrated that the anti-EGFR sdAbs could inhibit cancer cell growth in vitro and tumor growth in vivo. They could be potential therapeutics for the treatment of different human cancers.

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Humanization of Chimeric Anti-CD20 Antibody by Logical and Bioinformatics Approach with Retention of Biological Activity

Abstract: A humanized version of rituximab with potential to be developed into a biobetter for treatment of B-cell disorders has been successfully generated using a logical and bioinformatics approach.

Cited by 5 publications

References 41 publications

Biobetters in patients with immune-mediated inflammatory disorders: An international Delphi consensus

Biobetters in patients with immune-mediated inflammatory disorders: An international Delphi consensus

Generation of a Chimeric Antibody against a Synthetic Peptide Derived From IL-23p19 with Potential Therapeutic Application

Novel single-domain antibodies against the EGFR domain III epitope exhibit the anti-tumor effect

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