Summer Student Research Program
Project Description
FACULTY SPONSOR’S NAME AND DEGREE: Sergei Kotenko, Ph.D.
PHONE: (973) 972 - 3134
DEPARTMENT AND INTERNAL MAILING ADDRESS: Biochemistry; CC-H1228
E-MAIL: kotenkse@umdnj.edu
PROJECT TITLE (200 Characters max):
Generation and use of interleukin-10 inhibitors for cancer vaccination
HYPOTHESIS:
Many drugs and methods targeting tumors for destruction are constantly being developed and in
trials for their effectiveness. However, it is unlikely that a single drug equally effective in fighting
different cancers would be finally created, particularly because even a single tumor often represents a
pool of cells which have accumulated different multiple mutations. The immune system, on the other
hand, is the army of “universal soldiers” which ideally should be able to deal with any type of cancer. In
the case of cancers, however, the immune system is not able to handle it on its own and several strategies
have been developed to help the immune system to combat the disease. One of these strategies, the use of
therapeutic cancer vaccines, or so called active specific immunotherapies, was designed to activate the
immune system to treat existing tumors or prevent tumor recurrence. We think a successful ant-tumor
immunotherapy should combine two treatment modalities: activation of immune cells by
immunostimulatory cytokines such as interferons (IFNs) and inhibition of immunosuppressive cytokines
such as interleukin-10 (IL-10).
PROJECT DESCRIPTION (Include design, methodology, data collection, techniques, data analysis to be
employed and evaluation and interpretation methodology)
We recently demonstrated that melanoma cells that were modified to produce IFN-lambda
demonstrated reduced tumorigenicity in mouse model of melanoma growth. Using soluble IL-10 receptor
molecules we now would like to create a specific antagonist for murine IL-10 and test whether combined
delivery of IFN-lambda and an IL-10 inhibitor will further reduce tumorigenicity of melanoma cells.
With the use of gene engineering a student will create a unique heterodimeric soluble IL-10 receptor
molecule. The ability of this molecule to inhibit murine IL-10 will be tested in various in vitro
experiments. An expression plasmid encoding this molecule will be transfected into mouse B16
melanoma cells and clones expressing the molecule will be selected and later tested for their ability to
form tumors in mice. Long term objectives of the research are to treat and/or prevent cancer through the
enhancement of protective anticancer immunity and creation of cancer vaccines.
SPONSOR’S MOST RECENT PUBLICATIONS RELEVANT TO THIS RESEARCH:
Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer,
J.A., Sheikh, F., Dickensheets, H., and Donnelly, R.P. (2003) Interferon-λs mediate antiviral
protection through a unique class II cytokine receptor complex. Nat. Immunol. 4, 69-77
Lasfar, A., Lewis-Antes, A., Smirnov, S.V., Anantha, S., Abushahba, W., Tian, B., Reuhl, K.
Dickensheets, H., Donnelly, R.P., Raveche, E. and Kotenko, S.V. (2006) Characterization of the
Mouse IFN- Ligand-Receptor System: IFN-λs Exhibit Anti-Tumor Activity against B16
Melanoma. Cancer Res., 66, 4468-4477
IS THIS PROJECT SUPPORTED BY EXTRAMURAL FUNDS?
Yes
or
No
Summer Student Research Program
Project Description
(IF YES, PLEASE SUPPLY THE GRANTING AGENCY’S NAME)
THIS PROJECT IS:
Clinical
Laboratory
Behavioral
Other
THIS PROJECT EMPLOYS RADIOISOTOPES
THIS PROJECT INVOLVES THE USE OF ANIMALS
PENDING
APPROVED
IACUC PROTOCOL #
THIS PROJECT INVOLVES THE USE OF HUMAN SUBJECTS
PENDING
APPROVED
IRB PROTOCOL # M
WHAT WILL THE STUDENT LEARN FROM THIS EXPERIENCE?
The student will get familiar with cancer research, learn about animal models of tumor growth and
immunotherapy of cancer. He//she will acquire experience in following lab techniques: cloning,
expression vectors, cell culture procedure (growth and propagation of mammalian cells, transfection
and clone selection), gel shift and flow cytometry assays.