William J. Grimes, Ph.D.
Research

1. In collaboration with Dr. Evan Hersh and Dr. Doug Lake at the Arizona Cancer Center and the Department of Microbiology and Immunology, we have been studying antibodies produced by B-cells that infiltrate human tumors. The exciting observation is that many human tumors include B-cells that secrete anti-tumor antibody in vitro. Using methods developed by Doug Lake, a graduate student Hua Zhang was able to amplify, clone, and express a fragment of antitumor antibody (AZM1) that shows specificity for melanoma cells. We are pursuing studies on the nature of the antigen recognized and are also isolating B-cells from other kinds of cancer.

   References:

   Punt, C.J.A., J.A.M. Barbuto, W.J. Grimes., and E.M. Hersh. "Antitumor Antibody Produced by Human Tumor-infiltrating and Peripheral Blood B Lymphocytes." Cancer Imm. Immunother. 38, 225-231 (1994)

   Barbuto, J.A., Grimes, W.J. and E.M. Hersh." Antibodies to TNF: a component of B-cell immune responses with a role in tumor-host interaction." Cancer Imm. Immunother. 40, 31-36 (1995)

   Zhang, H., Lake, D.F., Barbuto, J.A., Bernstein, R.M., Grimes, W.J., and Hersh, E.M. "A Human Monoclonal Anti-melanoma Single Chain Fv(scFv) Antibody Derived from Tumor Infiltrating Lymphocytes." Cancer Research 55, 3584-3591 (1995)

2. Dr. Marjorie Smith and I have developed procedures for the PCR amplification, cloning, and Baculovirus expression of human HLA glycoproteins. Several undergraduates have played key roles in our studies, including Mike Kuhns (now a graduate student at Berkeley), Dawood Baradaran (now a medical student at U of A), Jackson Egen (a Senior in Biochemistry) and Tony Nuara (a Freshman in Biochemistry). The technology allows us to express large amounts of the HLA glycoproteins along with beta 2-microglobulin, and reconstitute bead bound peptides in vitro. Our goals in these studies are to identify anchor residues that determine the sequences of peptides that can be presented to the immune system by several alleles of the HLA. Our ultimate goal is to study the cytotoxic T-cell responses to peptides and their derivatives in human cancer patients and in HIV infected patients.

   References:

   Smith, M.H., Lam, K.S., Hersh, E.M., Lebl, M., and W.J. Grimes. "Peptide Sequences Binding to MHC Class I Proteins." Molecular Imm. 31, 1431-1437 (1994)