Biomaterial Database

Evaluation of CD20, CD22, and HLA-DR targeting for radioimmunotherapy of B-cell lymphomas. 2007

John M Pagel, and Anastasia Pantelias, and Nathan Hedin, and Shani Wilbur, and Laura Saganic, and Yukang Lin, and Donald Axworthy, and Donald K Hamlin, and D Scott Wilbur, and Ajay K Gopal, and Oliver W Press

Fred Hutchinson Cancer Research Center, University of Washington, and Aletheon Pharmaceuticals, Inc., Seattle, Washington 98109, USA. jpagel@fhcrc.org

Despite the promise of radioimmunotherapy using anti-CD20 antibodies (Ab) for the treatment of relapsed patients with indolent non-Hodgkin lymphoma (NHL), most patients treated with conventional doses of (131)I-tositumomab or (90)Y-ibritumomab eventually relapse. We did comparative assessments using conventional radioimmunotherapy targeting CD20, CD22, and HLA-DR on human Ramos, Raji, and FL-18 lymphoma xenografts in athymic mice to assess the potential for improving the efficacy of radioimmunotherapy by targeting other NHL cell surface antigens. Results of biodistribution studies showed significant differences in tumor localization consistent with variable antigenic expression on the different lymphoma cell lines. Interestingly, the radioimmunoconjugate that yielded the best tumor-to-normal organ ratios differed in each tumor model. We also explored administering all three (111)In-1,4,7,10-tetra-azacylododecane N,N',N'',N'''-tetraacetic acid antibodies in combination, but discovered, surprisingly, that this approach did not augment the localization of radioactivity to tumors compared with the administration of the best single radiolabeled Ab alone. These data suggest that conventional radioimmunotherapy using anti-CD20, anti-HLA-DR, or anti-CD22 Abs is effective when used singly and provides targeted uptake of radiolabel into the tumor that is dependent on the levels of antigen expression. Improvements in tumor-to-normal organ ratios of radioactivity cannot be achieved using directly labeled Abs in combination but may be afforded by novel pretargeting methods.

UI	MeSH Term	Description	Entries
D007205	Indium Radioisotopes	Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.	Radioisotopes, Indium
D008819	Mice, Nude	Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.	Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D002614	Chelating Agents	Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.	Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D005260	Female		Females
D005434	Flow Cytometry	Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.	Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006573	Heterocyclic Compounds, 1-Ring	Organic compounds that contain a ring structure made up of carbon and one or more additional elements such as nitrogen and oxygen.	Heterocyclic Cpds, 1-Ring,1-Ring Heterocyclic Compounds,1-Ring Heterocyclic Cpds,Heterocyclic Compounds, 1 Ring,Heterocyclic Cpds, 1 Ring
D006684	HLA-DR Antigens	A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.	HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000906	Antibodies	Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).