Drew Pardoll.M.D., Ph.D.
Co-PI Projects 4 and 5
Chair of Scientific
Committee for the
Secondary: Molecular Biology
Degree: M.D., Ph.D., Johns
Fax Number: 410-614-0549
E-mail address: email@example.com
School of Medicine Address:
JHU School of Medicine
720 Rutland Ave., 364 Ross
Baltimore, MD 21205
imunology, T cell tolerance; T cell regulation
Our laboratory focuses on
the regulation of antigen specific T cell responses and studies
approaches to modify these responses for immunotherapy. Specifically,
the interests of the laboratory fall into four areas:
1. Immunologic Tolerance -
the major mechanism by which tumors grow unchecked by the immune system
is their ability to induce tolerance among mature T cells. Our studies
using transgenic mouse models have indicated that the same mechanisms
that induce tolerance to peripheral tissue specific antigens likely are
responsible for tolerance induction to tumor antigens. In particular, we
have developed experimental evidence for the existence of a dedicated
bone marrow derived "tolerizing" antigen presenting cell (APC)
responsible for processing and presenting cell tissue and tumor antigens
to induce tolerance.
2. Antigen Presentation -
one of the cancer vaccine approaches that are being actively tested
clinically is the vaccination with tumor cells transduced with the GM-CSF
gene. These vaccines appear to be particularly potent because of the
ability of the locally produced GM-CSF to activate the differentiation
of bone marrow progenitors into dendritic cells. Using subtractive
library approaches, we have been in the process of mapping out genes
unique to dendritic cells that mediate their potent T cell stimulatory
3. Definition of
Immunodominant and Immunorelevant Tumor Antigens - Ultimately, we wish
to define the biological and biochemical rules that determine which
antigens are dominant targets for immune responses. We are currently
using genomic approaches to rapidly screen for genes encoding antigens
recognized by tumor specific T cells.
4. Dissection of Immunologic
Effector Pathways - Our studies on GM-CSF gene modified tumor vaccines
have led to the identification of novel effector pathways in tumor
immunity. Besides the classical CTL response, we have found that
activation of the eosinophils and activation of macrophages to produce
NO and superoxides are critical pathways of tumor killing. Using in
vitro systems for the chemical generation of these mediators, we have
been defining molecular pathways by which these mediators specifically
induce apoptosis in tumor cells.
1.Wang, T.-L., Ling, M.,
Shih, I.-M., Pham, T., Pai, S.I., Lu, Z., Kurman, R.J., Pardoll, D.M.,
and Wu, T.-C. (2000) Intramuscular administration E7-transduced
dendritic cells generate the most potent E7-specific antitumor immunity.
Gene Therapy, 7:726.
2. Ewend M.G., Thompson, R.C.,
Anderson, R., Sills, A.K., Stavely-O'Carroll, K., Tyler, B.M., Hanes,
J., Brat, D., Thoams, M., Jaffee, E.M., Pardoll, D.M., and Brem, H.
(2000). Intracranial paracrine IL-2 therapy stimulates prolonged
antitumor immunity which extends outside the central nervous system. J
Immunotherapy Jul-Aug 23(4):438-448.
3. Chen, C.-H., Wang, T.-L.,
Hung, C.-F., Yang, Y., Pardoll, D.M., and Wu, T.-C. (2000) Boosting with
recombinant vaccinia increased HPV E7-specific T cell precursor
frequencies of HPV-16 E7-expressing DNA vaccines. Vaccine,
4. Pardoll, D.M. (2000)
Therapeutic vaccination for cancer. Clinical Immunology 95:S44-S62.
5. Slansky, J.E., Rattis,
F.M., Boyd, L.F., Fahmy, T., Jaffee, E.M., Schneck, J.P., Margulies, D.H.,
and Pardoll, D.M. (2000) Enhanced antigen-specific antitumor immunity
with altered peptide ligands that stabilize the MHC-peptide-TCR complex.
Immunity Oct 13:529-538.