NDLI: Structure Based Refinement of a Humanized Monoclonal Antibody That Targets Tumor Antigen Disialoganglioside GD2

Content Provider	PubMed Central
Author	Ahmed, Mahiuddin Hu, Jian Cheung, Nai-kong V.
Copyright Year	2014
Abstract	Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antibody 3F8, the highest affinity anti-GD2 antibody in clinical development. Two constructs (V3 and V5) were designed to enhance stability and minimize potential immunogenicity. Construct V3 contained 12 point mutations and had higher thermal stability and comparable affinity and in vitro tumor cells killing as the parental hu3F8. Construct V5 had nine point mutations to minimize potential immunogenicity, but resulted in weaker thermal stability, weaker antigen binding, and reduced tumor killing potency. When construct V3 was combined with the single point mutation HC:G54I, the resulting V3-Ile construct had enhanced stability, antigen binding, and a nearly sixfold increase in tumor cell killing. The resulting product is a lead candidate for clinical development for the treatment of GD2-positive tumors.
Related Links	http://dx.doi.org/10.3389/fimmu.2014.00372
Starting Page	372
File Format	PDF
ISSN	16643224
e-ISSN	16643224
Journal	Frontiers in Immunology
Volume Number	5
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2014-08-01
Access Restriction	Open
Rights Holder	Frontiers Media S.A.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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