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dc.contributor.authorPark, Spencer
dc.date.accessioned2017-04-04T20:27:59Z
dc.date.available2017-04-04T20:27:59Z
dc.date.issued2017-01-30
dc.identifier.otherPark_cornellgrad_0058F_10003
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:10003
dc.identifier.otherbibid: 9906083
dc.identifier.urihttps://hdl.handle.net/1813/47836
dc.description.abstractMuch attention has been given to the molecular and cellular pathways linking inflammation with cancer and the local tumor environment to identify new target molecules that could lead to improved diagnosis and treatment. Among the many molecular players involved in the complex response, central to the induction of inflammation is intercellular adhesion molecule (ICAM)-1, which is of particular interest for its highly sensitive and localized expression in response to inflammatory signals. ICAM-1, which has been implicated to play a critical role in tumor progression in various types of cancer, has also been linked to cancer metastases, where ICAM-1 facilitates the spread of metastatic cancer cells to secondary sites. This unique expression profile of ICAM-1 throughout solid tumor microenvironment makes ICAM-1 an intriguing molecular target, which holds great potential as an important diagnostic and therapeutic tool. Herein, we have engineered the ligand binding domain, or the inserted (I) domain of a leukocyte integrin, to exhibit a wide range of monovalent affinities to the natural ligand, ICAM-1. Using the resulting I domain variants, we have created drug and gene delivery nanoparticles, as well as targeted immunotherapeutics that have the ability to bind and migrate to inflammatory sites prevalent in tumors and the associated microenvironment. Through the delivery of diagnostic agents, chemotherapeutics, and immunotherapeutics, the following chapters demonstrate that the affinity enhancements achieved by directed evolution bring the affinity of I domains into the range optimal for numerous applications.
dc.language.isoen_US
dc.subjectintegrin
dc.subjectImmunology
dc.subjectBiomedical engineering
dc.subjectnanoparticle
dc.subjectNanotechnology
dc.subjectCAR-T
dc.subjectICAM-1
dc.subjectcancer
dc.titleAffinity-tuning leukocyte integrin for development of safe therapeutics
dc.typedissertation or thesis
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Biomedical Engineering
dc.contributor.chairJin, Moonsoo
dc.contributor.committeeMemberZarnegar, Rasa
dc.contributor.committeeMemberKing, Michael R.
dcterms.licensehttps://hdl.handle.net/1813/59810
dc.identifier.doihttps://doi.org/10.7298/X4TH8JPH


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