A novel monobody-drug conjugate to treat mutant KRas pancreatic cancer.
A novel monobody-drug conjugate to treat mutant KRas pancreatic cancer.
批准号:
10323748
负责人:
DAFNA BAR-SAGI
金额:
$39.87万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-01 至 2023-05-31
关键词:
AddressAntibody-drug conjugatesApoptosisAttentionBiologic CharacteristicBiologicalBiological AssayBiotechnologyBlood VesselsCancer Cell GrowthCancer cell lineCell LineCharacteristicsClinicClinical TrialsDataDendritic CellsDevelopmentDiseaseDoseDrug Delivery SystemsEndotheliumEquus caballusEvaluationEventExtracellular ProteinFDA approvedFibronectinsFutureGovernmentHealthHumanIn VitroIncidenceIntellectual PropertyKPC modelKnowledgeLaboratoriesLeadLesionLicensingLiposomesLiquid substanceLungMalignant NeoplasmsMalignant neoplasm of pancreasMaximum Tolerated DoseMetabolicMetastatic Neoplasm to the LiverMorbidity - disease rateNatureNeoplasm MetastasisNew YorkNormal CellOncogenesPaclitaxelPancreatic Ductal AdenocarcinomaPatientsPenetrationPersonsPharmaceutical PreparationsPhasePreclinical TestingProcessProteinsProtocols documentationRenal functionResearch PersonnelResourcesSafetySerumSmall Business Innovation Research GrantSmall Business Technology Transfer ResearchSolubilitySpecificityTechnologyTherapeuticTissuesToxic effectUniversitiesXenograft procedureaustinbasecancer cellcancer typecellular targetingclinically relevantcommercializationcompanion diagnosticscytotoxicdrug candidateefficacy studyexpectationexperiencefirst-in-humanimprovedin vivoin vivo Modelinnovationirinotecanliver functionmacrophagemortalitymouse modelmutantnanomolarnanoparticleneoplastic cellneutrophilnovelnovel therapeuticspancreatic cancer cellspancreatic cancer modelpancreatic ductal adenocarcinoma modelpremalignantprogramsstandard of caresynthetic proteinsystemic toxicitytherapeutic developmenttherapeutically effectivetumortumor progressionvalidation studies
中文摘要
项目概述:TEZCAT实验室有限责任公司是一家早期的奥斯汀生物技术公司
英文摘要
Project Summary: TEZCAT Laboratories LLC is an early-stage, Austin-based biotechnology
company developing novel biologics with a unique mechanism of action to treat the most
recalcitrant cancers, such as mutant KRas pancreatic cancer. As an alternative to targeting
mutant KRas itself, much attention has been paid to targeting cellular events that are a result of
mutant KRas. New efforts are underway to exploit previously unrecognized vulnerabilities. We
have observed that mutant KRas pancreatic cancer cells display high levels of a protein
scavenging process. Harnessing this metabolic adaptation, we have created protein-drug
conjugates that carry an FDA-approved cytotoxic payload. In vitro and in vivo assays demonstrate
that the protein-drug conjugates show selectivity for mutant KRas cancer cells and maintain
potency in the low nanomolar range. The protein-drug conjugates display relatively fast systemic
clearance but maintain beneficial characteristics of biologics such as decreased systemic
toxicities and tumor accumulation. Thus, we hypothesize that our novel conjugates will reduce
on-target and off-target effects often seen with traditional antibody-drug conjugates and fill a void
of therapeutic options for patients with mutant KRas pancreatic cancer. We propose a Phase I
STTR program for investigators at TEZCAT Laboratories and New York University Langone
Health to advance this lead through Specific Aims that evaluate the lead drug candidates in
controlling human cancer cell growth in a clinically-relevant mouse model of pancreatic cancer.
TEZCAT Laboratories is working with NYU to facilitate licensing the underlying intellectual
property covering the technology being developed. The commercialization strategy will be based
on establishing initial efficacy and nontoxicity of the lead compound in relation to mutant KRas
status in Phase I STTR studies, further development towards IND status in Phase II SBIR studies,
and then first-in-human clinical trials. Thus, we expect Phase I STTR to provide the basis for
pursuit of additional data in Phase II aimed at GMP protocols and further non-GLP and GLP safety
and toxicity studies.
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会议论文
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