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T Cell Immunology
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
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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
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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
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Recent
Publications
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.
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