Patient-derived heavy chain antibody targets cell surface HSP90 on breast tumors

BMC Cancer
Charan V DevarakondaKevin P Claffey

Abstract

Monoclonal antibodies have been used to effectively treat various tumors. We previously established a unique strategy to identify tumor specific antibodies by capturing B-cell response against breast tumor antigens from patient-derived sentinel lymph nodes. Initial application of this approach led to identification of a tumor specific single domain antibody. In this paper we optimized our previous strategy by generating heavy chain antibodies (HCAbs) to overcome the deficiencies of single domain antibodies. Here we identified and characterized a heavy chain antibody (HCAb2) that targets cell surface HSP90 antigen on breast tumor cells but not normal cells. Eight HCAbs derived from 4 breast cancer patients were generated using an in vitro expression system. HCAbs were screened against normal breast cells (MCF10A, HMEC) and tumor cell lines (MCF7, MDA-MB-231) to identify cell surface targeting and tumor specific antibodies using flow cytometry and immunofluorescence. Results observed with cell lines were validated by screening a cohort of primary human breast normal and tumor tissues using immunofluorescence. Respective antigens for two HCAbs (HCAb1 and HCAb2) were identified using immunoprecipitation followed by mass spectrometr...Continue Reading

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Citations

Feb 11, 2018·Cancer Immunology, Immunotherapy : CII·Jonathan R McDanielDavid N Krag
Oct 18, 2019·Current Molecular Pharmacology·Samira BahramiAmirhossein Sahebkar
Sep 30, 2020·Expert Opinion on Therapeutic Patents·Li LiXiao-Li Xu
Mar 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ruizhi WangXiaolin Wang
Apr 6, 2021·Frontiers in Immunology·Zarema AlbakovaAlexander Sapozhnikov

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Methods Mentioned

BETA
xenograft
PCR
immunoprecipitation
immunoprecipitation assay
pull down
flow cytometry
surgical resection
immunoprecipitations
protein folding

Software Mentioned

QUEST
Pro
GraphPad Prism
FlowJo
Adobe Photoshop
ZEN
Pro Plus
Mascot
Image

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