IGF::OT::IGF Topic 372: Development and Validation of Canine scFvs for Pre-Clinical Development of Targeted Therapeutics - Moonshot
IGF::OT::IGF Topic 372: Development and Validation of Canine scFvs for Pre-Clinical Development of Targeted Therapeutics - Moonshot
批准号:
9915565
负责人:
Brendan Pucell
金额:
$5.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-17 至 2019-07-15
关键词:
AffinityAnimal Cancer ModelAntibodiesBindingCD19 geneCD3 AntigensCTLA4 geneCanis familiarisCell LineCellsDevelopmentDiagnosticFlow CytometryGoalsHumanImmune TargetingImmunohistochemistryImmunologicsImmunology procedureImmunotherapeutic agentIn VitroLeadLibrariesLymphomaMalignant NeoplasmsMonoclonal AntibodiesPennsylvaniaPhage DisplayProductionReagentSmall Business Innovation Research GrantSpecificityTherapeutic UsesTissuesUniversitiesValidationVeterinary MedicineVeterinary SchoolsWorkbasecancer immunotherapychimeric antigen receptor T cellsclinically relevantcost effectivein vivopreclinical developmentresponse biomarkertargeted treatment
中文摘要
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英文摘要
The goal of this SBIR is to provide proof-of-concept of Vetigenics’ canine-derived scFv phage display platform for rapid, cost effective production of highly versatile, canine-derived scFvs. scFvs against CD19, CD3 and CTLA4, three high-value, immunological molecules being targeted by antibody-based strategies in human cancer immunotherapy, will be isolated. Selected scFvs will be sequenced and binding affinities determined. Through its collaborators at the University of Pennsylvania School of Veterinary Medicine, Vetigenics has access to canine cells, cell lines and tissues providing an unparalleled ability to validate isolated scFv. Target specificity and functionality of isolated scFvs will be validated using standard immunological assays. To demonstrate the versatility and broad applicability of the scFv format, a lead canine CD19-specific scFv will be selected and used to generate 1) canine CAR T cells and 2) monoclonal antibodies. CD19-specific scFv formats will be validated for specificity, functionality and in vitro diagnostics including flow cytometry and immunohistochemistry. Successful completion of this work will provide validated reagents for in vivo use in dogs with cancer, enabling exploration of combination approaches and correlative biomarkers of response in a clinically relevant large animal cancer model. In addition, this work will provide parallel promising immunotherapeutics for the veterinary market.
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