Research: Laboratory Program –
M. Jules Mattes, Ph.D.

Dr. Mattes is currently an Associate Member at GSCC. He received his Ph.D. from the Massachusetts Institute of Technology in 1977, was a Post-doctoral Fellow at the National Cancer Institute for 3 years, and a Research Associate at Memorial Sloan-Kettering Cancer Center for 5 years under Dr. Kenneth O. Lloyd. He joined GSCC in 1985. His work is currently funded by the National Institutes of Health and the Department of Energy.

Dr. Mattes's research is aimed at the development of strategies to use monoclonal antibodies (Abs) for cancer therapy. The work has included studies to identify the optimal Abs and the optimal Ab-conjugates. Ab-conjugates that have been tested include those with radioactive isotopes, toxic drugs, and protein toxins. Since animal experiments play a critical role in the development of effective clinical methods, he has also developed and characterized new animal models, in which human cancer cells are grown in immunodeficient mice. The type of tumor investigated has been primarily B-cell lymphoma, but studies are also being conducted with melanoma and carcinomas of various types.

A major focus has been the comparison of different radioactive isotopes, especially isotopes that emit low energy electrons. Dr. Mattes demonstrated for the first time that such radiolabels conjugated to Abs can kill cells in vitro efficiently and specifically, with 100% kill at sufficient Ab concentrations. These conjugates were shown to have greater specificity than conjugates with beta-particle emitters (which emit electrons of much higher energy) that have been used in nearly all previous studies in this area. In an animal model, the same conjugates were found to cure mice having disseminated cancer. The most promising isotope appears to be ⁶⁷Gallium, but this point is being further investigated.

Another major project has been to investigate the intracellular uptake of Abs after binding to the cell surface, as well as the processing of the Ab after internalization. An anti-CD20 Ab (reactive with B-cell lymphomas) was shown to be internalized into a subcellular compartment called the endocytic recycling compartment, which was not previously known. Thus this Ab should be able to deliver drugs or toxins into the cancer cells where they can be most effective.

1. Ong GL, Goldenberg DM, Hansen HJ, and Mattes MJ. Cell surface expression and metabolism of MHC class II invariant chain (CD74) by diverse cell lines. Immunology 98: 296-302 (1999).
2. Ong GL and Mattes MJ. Processing of antibodies to the MHC class II antigen by B-cell lymphomas: release of Fab-like fragments into the medium. Molec Immunol 36: 777-788 (1999).
3. Shih L, Ong GL, Burton J, Mishina D, Goldenberg DM, and Mattes, MJ. Localization of an antibody to CD74 (MHC class II invariant chain) to human B-cell lymphoma xenografts in nude mice. Cancer Immunol Immunother 49: 208-216 (2000).
4. Govindan SV, Goldenberg DM, Elsamra SE, Griffiths GL, Ong GL, Brechbiel MW, Burton J, Sgouros, G, and Mattes MJ. Radionuclides linked to a CD74 antibody (LL1) as therapeutic agents for B-cell lymphoma: comparison of Auger electron emitters with -particle emitters. J Nuclear Med 41: 2089-2097 (2000).
5. Ong GL, Elsamra SE, Goldenberg DM, and Mattes MJ. Single-cell cytotoxicity with radiolabeled antibodies. Clin Cancer Res 7: 192-201 (2001).
6. Ochakovskaya R, Osorio L, Goldenberg DM, and Mattes MJ. Therapy of disseminated B-cell lymphoma xenografts in severe combined immunodeficient mice with an anti-CD74 antibody conjugated with 111Indium, ⁶⁷Gallium, or ⁹⁰Yttrium. Clin Cancer Res 7: 1505-1510 (2001).