Mechanisms of Heterogeneous Transport of Monoclonal         Antibodies in Tumors
{'Code': '07020000', 'Directorate': {'Abbreviation': 'ENG', 'LongName': 'Directorate For Engineering'}, 'Division': {'Abbreviation': 'CBET', 'LongName': 'Div Of Chem, Bioeng, Env, & Transp Sys'}}
{'SignBlockName': 'Dov Jaron', 'PO_EMAI': None, 'PO_PHON': None}
The overall objective of this work is to measure experimentally and to          analyze mathematically the relative contributions of various                    mechanisms of transport of monoclonal antibodies (MAbs) in a tumor.             Experiments will involve direct measurement of spatial distributions            of (i) blood perfusion rate, (ii) interstitial pressure, (iii)                  antigen, and (iv) antibody at various times post-injection in a tumor.          The tumor will be grown as a standard implant subcutantously, and as            an "isolated-tumor" connected to the host with a single artery and a            single vein.  The latter preparation will permit direct measurement of          interstitial fluid velocity at the tumor periphery.  To discern the             role of binding, two types of antibodies will be used:  a non-specific          antibody and a hepatoma specific antibody.  The resulting data will be          analyzed by developing two physiologically-based distributed parameter          models:  (i) a fluid transport model and (ii) a solute transport                model.  The former will permit calculations of interstitial pressure            and interstitial velocity in a tumor, and the latter will permit                calculations of the spatial and temporal distribution of MAbs in a              tumor.  Extensive simulations and sensitivity analyses will be carried          out to suggest ways of improving MAb delivery and distribution in               tumors.                                                                                                                                                         If MAbs are to fulfill their promise, methods must be developed to              deliver them selectively and in adequate quantities to their                    target in the body.  Unfortunately, MAbs have shown limited or no               success in cancer treatment primarily due to their inability to                 penetrate solid tumors uniformly.  In particular, when MAbs are                 injected into the blood stream, very low amounts accumulate in                  the center of a solid tumor.  There is a preferential                           distribution of MAbs in areas closest to the functional blood                   vessels and, in many cases, on the tumor periphery.  An abundance               of antibody at the tumor periphery may be helpful in the tumor                  detection using radioimaging techniques, but it has no                          therapeutic effect against cells in the center.  After the outer                cells have been killed, the residual tumor grows back again.  The               engineering approach used for identifying and understanding the                 mechanisms governing the heterogeneous distribution in tumors may               suggest novel approaches to deliver antibodies and other                        macromolecules to all regions of a tumor.
{'FirstName': 'Rakesh', 'LastName': 'Jain', 'PI_MID_INIT': 'K', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Rakesh K Jain', 'EmailAddress': None, 'NSF_ID': '000237802', 'StartDate': '02/01/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Carnegie-Mellon University', 'CityName': 'PITTSBURGH', 'ZipCode': '152133815', 'PhoneNumber': '4122688746', 'StreetAddress': '5000 FORBES AVE', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Pennsylvania', 'StateCode': 'PA', 'CONGRESSDISTRICT': '18', 'CONGRESS_DISTRICT_ORG': 'PA18', 'ORG_UEI_NUM': 'U3NKNFLNQ613', 'ORG_LGL_BUS_NAME': 'CARNEGIE MELLON UNIVERSITY', 'ORG_PRNT_UEI_NUM': 'U3NKNFLNQ613'}
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[{'Code': '1402', 'Text': 'BIOCHEMICAL & BIOMASS ENG'}, {'Code': '1414', 'Text': 'INTERFAC PROCESSES & THERMODYN'}]
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