Project: Research project

Project Details


The long term goals described in this physician-scientist grant proposal
are to learn the hybridoma technology and apply it to the radiologic and
scintigraphic diagnosis of disease. The application of monoclonal
antibodies currently being used in Nuclear Medicine is limited by
immunogenicity, relatively low affinity, and inherent limitations in
pharmacokinetics. In the past, analysis of factors that affect antibody
targeting has been hampered ny inability to control for the effect of
numerous confounding variables. By utilizing the extremely modifiable
model target which we have created, behavior of families of modified
antibodies can be compared in a rigorous manner. In this way, we intend
to systematically analyze the effect of affinity, avidity, half-life,
class and subclass, antigen density and circulating antigen in order to
understand the contribution of these factors to antibody targeting and
imaging. Initially, families of closely related mouse monoclonals
different classes and with different affinities and avidities will be used
to determine whether higher binding will significantly increase their
effectiveness in targeting and imaging of haptenated beads. Subsequently,
mutant antibodies generated by somatic cell genetics and recombinant DNA
technology will be evaluated. Once the optimal characteristics of
antibodies for targeting have been defined, SCID mice populated with human
lymphoid cells will be investigated for use in generating human monoclonal
antibodies with these attributes. In this way, we hope to produce
optimized monoclonal antibodies for ultimate use in Nuclear Medicine
diagnosis and therapy.
Effective start/end date7/5/906/30/95


  • Immunology
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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