Dr. James W. Rohrer, Associate Professor, graduated with a B. A. in Zoology from the University of Kansas in 1969 and received his Ph. D. in Microbiology from the University of Kansas in 1975. He carried out his postdoctoral study at Washington University School of Medicine in the Department of Pathology under Dr. Richard G. Lynch. Dr. Rohrer was awarded a National Cancer Institute Postdoctoral Fellowship and a Leukemia Society of America Special Fellowship during his postdoctoral training. He joined the faculty at the University of South Alabama College of Medicine in 1979.
My laboratory is characterizing the T and B lymphocyte response to immature laminin receptor protein (iLRP) during tumorigenesis. ILRP was previously denoted by us oncofetal antigen (OFA). ILRP is a 32-44 kdalton protein which is present in the monomeric form on early to midgestational fetal cells and on all tumor cells we have tested in man, mouse, rat, and hamster. Normal neonatal and adult cells express an acylated dimer form of LRP (mature LRP) which is not seen by the immune system. However, iLRP is immunogenic and iLRP-specific T cells are activated during induction of lymphomas in sub-lethally irradiated mice. Similarly, iLRP-specific T cells are activated during chemical carcinogen induction of fibrosarcomas in mice. Also, growth of already-preinduced tumors in mice will induce activation of iLRP-specific T cells. Effector T cells specific for iLRP and capable of killing iLRP-specific tumor cells or inducing activation of tumoricidal macrophages are induced during tumor development. However, regulatory iLRP-specific T cells which secrete IL-10 are also induced. IL-10 inhibits the ability of cytotoxic T cells to kill the iLRP-expressing tumor cells and thus can lead to enhanced tumor growth. The same types of iLRP-specific T cells are induced during human breast carcinoma development. Anti-iLRP IgG is also produced during tumor development. ILRP is expressed early after transformation of tumor cells, is required for tumor metastasis, and is highly conserved evolutionarily. Immunization of mice with recombinant iLRP induces protection from tumor challenge, induction of effector and regulatory T cells, and anti-iLRP IgG depending on the dose of iLRP used for immunization. It appears that the ratio or time of appearance of effector to regulatory T cells determines how aggressive the developing tumor will be and, in humans, how effective treatment will be. I am now determining the epitopes regulatory and effector T cells recognize to see if immunization with an appropriately truncated protein will induce only effector T cells and thus maximize immunotherapeutic and protective use of anti-iLRP immunity. I am also determining the role of the various types of iLRP-specific T cells, anti-iLRP IgG, and IL-10 in minimizing metastasis and invasion of tumor cells in appropriately iLRP-immunized mice. Because mature LRP is not expressed in a form recognized by the immune system, whereas iLRP is immunogenic for protective T cells plus is involved in tumor metastasis, study of the T cell and B cell immune response to iLRP during tumorigenesis may allow optimizing that immunity such that iLRP can be used as a vaccine target or immunotherapy target.
J. W. Rohrer, A. L. Barsoum, and J.
H. Coggin, Jr. The development of a new universal tumor rejection
antigen expressed on human and rodent cancers for vaccination, prevention
of cancer, and anti-tumor therapy. Mod. Asp. Immunobiol. 2001; 1:191-195.
C. Zelle Rieser, A. L. Barsoum, F. Sallusto, R. Ramoner, J. W. Rohrer, L. Holtl, G. Bartsch, J. H. Coggin Jr., and M. Thurnher. Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma. J Urol 2001; 165:1705-1709.
J. W. Rohrer, A. L. Barsoum, D. L. Dyess, J. A. Tucker, and J. H. Coggin, Jr. Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes. J. Immunol 1999; 162:6880-6892
Coggin, J. H., Jr., A. L. Barsoum, J. W. Rohrer. 37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. Anticancer Res. 1999; 19:5535-5542
J. W. Rohrer, C. Culpepper, A. Barsoum, and J. H. Coggin, Jr. Characterization of RFM mouse T lymphocyte anti-OFA immunity in apparent tumor free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning. J. Immunol. 1995; 154:2266-2280.
J. W. Rohrer and J. H. Coggin, Jr. Non-cytotoxic CD8 T cell clones inhibit anti-tumor T cell function by secreting IL-10. J. Immunol. 1995; 155:5719-5727.
| Phone: | (251) 460-6326 | |
|---|---|---|
| FAX: | (251) 460-7269 | |
| E-mail: | jrohrer@jaguar1.usouthal.edu |