High throughput camelid antibody screening as a drug discovery platform
高通量骆驼抗体筛选作为药物发现平台
基本信息
- 批准号:9746340
- 负责人:
- 金额:$ 17.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-01 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAfricaAgreementAnimal ModelAnimalsAntibodiesAntibody FormationAntibody TherapyAntigensAsiaBindingBiological AssayBispecific AntibodiesCD19 geneCD3 AntigensCaliforniaCatalytic AntibodiesCell LineCitiesClinical ResearchClinical TrialsCollaborationsCommunicable DiseasesContractsDevelopmentDiagnosticDiseaseDisease OutbreaksDisease modelERBB2 geneEmerging Communicable DiseasesEpidermal Growth Factor ReceptorEpitope MappingEscape MutantFeesFundingFutureGenerationsGenesGoalsGovernmentHemagglutininHumanImmunizationImmunoglobulin GIn VitroIndividualInfectionInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza A Virus, H7N9 SubtypeInfluenza A virusInstitutionLibrariesLicensingMDCK cellMalignant NeoplasmsMonoclonal AntibodiesMutationNamesNeuraminidasePassive ImmunizationPharmacologic SubstancePhasePlaque AssayPrivatizationProductionResearchSecureSpecificitySurfaceSystemT-LymphocyteTechnologyTestingTherapeuticTherapeutic antibodiesTimeToxinUniversitiesUtahValidationViralVirusVirus DiseasesVisionWorkXenograft procedureYeastsZoonosesanti-canceranti-influenzaantibody librariesbasecancer therapyclinical applicationcommercial applicationcommercializationcost effectivedrug discoveryexperimental studyhuman diseasehumanized antibodyimmunogenicimprovedin vitro Assayin vivoinfectious disease treatmentinfluenzavirusnanobodiesnew therapeutic targetnovelnovel strategiespaymentprogramsscale upscreeningsuccesstherapeutic targettumor
项目摘要
ABSTRACT. Monoclonal antibodies are used for treatment of a wide range of diseases from cancer to
infectious diseases. However, development of antibodies with high affinity and specificity is still time-
consuming, labor-intensive and unpredictable, especially to low immunogenic or toxic targets. A new approach
for rapid development of antibodies against a variety of diseases, especially against emerging diseases is
much needed.
Abzyme Therapeutics LLC is actively developing animal-free antibody discovery platforms to accelerate
generation of diagnostic and therapeutic antibodies. Phase I objectives have been successfully completed.
Specifically, we have created a so-called yeast surface display camelid Self-Diversifying VHH Antibody Library
or SDALib as a monoclonal antibody generating system providing a diverse array of antibodies in vitro, without
using in vivo immunization. The main feature of the system is the ability to self-generate a library with
diversified antibodies by means of hypermutation induction in antibody encoding genes. As proof-of-principle,
we have successfully used the platform to isolate a set of single-domain antibodies against N1 neuraminidase
(NA) derived from influenza H5N1 virus. Obtained VHH antibodies have been shown to express efficiently in a
bacterial system providing an opportunity for accelerated scale-up of antibody production for therapeutic
application. Anti-NA VHH antibodies have been purified and characterized in in vitro assays. As proof of
principle one (Flu27-8) out of several anti-NA VHH antibodies, that is reactive with N1 NAs of both H5N1 and
H1N1 influenza viruses, has been humanized preserving the full anti-NA activity of the parental molecule. Bi-
valent anti-NA antibodies that have been produced in a bacterial system as linear fusions showed a significant
increase in antibody activity in in vitro assays.
Subsequent efforts of Phase II consist of three specific aims that will be performed simultaneously: (i) advance
the N1 anti-NA antibodies isolated in Phase I toward clinical application by demonstrating both in vitro and in
vivo activity against H5N1 and H1N1 influenza viruses; (ii) expand the application of the platform for
developing antibodies targeting both hemagglutinin and NAs of other influenza virus subtypes, e.g. H3N2 and
H7N9 which have unusual zoonotic potential and aiming for antibodies cross-reacting with several different
neuraminidases (H5N1, H1N1, H3N2 and H7N9); (iii) utilize the antibody discovery platform for developing
VHH antibodies against a set of cancer targets followed by production of novel IgG-like VHH-based bispecific
humanized antibodies. Phase II efforts are to further extend the application of the technology for rapid
development of novel antibodies to therapeutic targets and to advance humanized anti-influenza antibodies
isolated in phase I into clinical studies.
摘要。单克隆抗体用于治疗多种疾病,从癌症到
项目成果
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High throughput camelid antibody screening as a drug discovery platform
高通量骆驼抗体筛选作为药物发现平台
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$ 17.03万 - 项目类别:
High throughput camelid antibody screening as drug discovery platform
作为药物发现平台的高通量骆驼抗体筛选
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8647986 - 财政年份:2014
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$ 17.03万 - 项目类别:
Nanobodies for detecting and manipulating A to I editing enzymes and their modified RNA products
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- 资助金额:
$ 17.03万 - 项目类别:
High throughput camelid antibody screening as a drug discovery platform
高通量骆驼抗体筛选作为药物发现平台
- 批准号:
9139772 - 财政年份:2014
- 资助金额:
$ 17.03万 - 项目类别:
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