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Jeffrey S. Miller, M.D.
Professor
Department of Medicine
Northwestern University School of Medicine, 1985, M.D.
mille011@tc.umn.edu
612-625-7409 office
612-626-4217 lab
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Research Interests:
Natural killer cell development
Dr. Miller's research team works in two areas that seek to understand
fundamental issues regarding innate immune function: 1.) How undifferentiated
stem cells develop into functioning NK cell lymphocytes, and 2.) How to
manipulate NK cells to treat or prevent cancer relapse. A major emphasis
is on natural killer (NK) cell development and the mechanism of commitment
to the lymphoid versus myeloid lineages. Recently, receptors on NK cells
have been identified that recognize class I MHC molecules. The hypothesis
underlying current research efforts is that "self" MHC molecules influence
the NK cell receptor repertoire during development. These NK cell receptors
may also play a physiologic role in cancer. Laboratory evaluation and
human clinical trials will test the hypothesis that a mismatch between
NK receptor and class I alleles on recipient tumor will result in greater
tumor kill.
Targeted Immunotherapy to Treat Human Cancer
The second major emphasis in Dr. Miller's laboratory is based on pre-clinical
and clinical studies to develop effective anti-tumor immunotherapies.
Early studies focused on nonspecific immune stimulation using subcutaneous
IL-2. Strong evidence suggests that this nonspecific therapy alone will
be ineffective and current efforts aim to target effectors specifically
to tumor cells. For natural killer cells, current approaches include combined
therapy with monoclonal antibodies and interleukin-2 to target therapy
through antibody dependent cellular cytotoxicity (ADCC). To target T-cells,
we have initiated a study in collaboration with Matthew Mescher (Director,
Center for Immunology). These studies focus on the human translation of
large multivalent immunogens (LMI) into the clinic. Our first clinical
trial was FDA approved and open for accrual in April, 2001. Patients with
advanced renal cell carcinoma and melanoma are eligible. Additional trials
are planned for breast cancer. Understanding immune integrity in cancer
patients is an integral part of this effort.
Selected Recent Publications:
- Miller, J.S. Soignier Y. Panoskaltsis-Mortari A., McNearney S.A., Yun G.H..,
Fautsch S.K., McKenna D., Le C., Defor T.E., Burns L.J., Orchard P.J., Blazar B.R.,
Wagner J.E., Slungaard A., Weisdorf D.J., Okazaki I.J., McGlave P.B. 2005. Successful
adoptive transfer and in vivo expansion of human haploidentical NK cells
in cancer patients. Blood, 105:3051-3057.
- Miller J.S., Curtsinger J., Berthold M., Malvey K., Bliss R.L., Le C.T., Fautsch
S.K., Dudek A.Z., Blazar B.R., and Panoskaltsis-Mortari A. 2005. Diminished
neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in
patients after treatment with chemotherapy or hematopoietic cell
transplantation. Clinical Immunology, 117:144-151.
- Cooley S., McCullar V., Wangen R., Bergemann, T.L., Spellman S., Weisdorf D.J.,
and Miller J.S. 2005. KIR reconstitution is altered by T cells in the graft and
correlates with clinical outcomes after unrelated donor transplantation.
Blood, 106:4370-4376.
Last modified on August 9, 2006
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