Download B. Positions and Honors

OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME:
Eli Gilboa
POSITION TITLE:
Professor of Immunology & Mirobiology
eRA COMMONS USER NAME (credential, e.g., agency login)
:E.GILBOA
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency
training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
Completion Date
MM/YYYY
FIELD OF STUDY
Hebrew University, Jeruasalem, Israel
B.Sc
1971
Biochemistry
Weizman Institute, Rehovot, Israel
Ph.D.
1977
Molecular Biology
M.I.T., Cambridge, MA, USA
Post-doc
1980
Retroviruses
A. Personal Statement
I am a translational investigator and have made important contributions in the fields of gene therapy, HIV
research, and cancer immunotherapy. Supported by constant peer-reviewed funding from NIH and from nonNIH agencies, I have introduced novel concepts that helped shape these fields, such as the use of “selfinactivating” retroviral vectors, HIV TAR decoys, mRNA transfected DC vaccines, or targeting tumor stromal
antigens. Recently, my lab has pioneered the use of oligonucleotide-based aptamer ligands to modulate tumor
immunity that serves the foundation of this proposal. I have introduced new concepts in cancer immunotherapy
such as enhancing the antigenicity of disseminated tumor lesions (1), promoting immune memory (3), or
targeting costimulation to the tumor lesion (2, 4). I have developed expertise in aptamer technology, in large
part thru establishing a “consortium” of leading investigators in this new field that meets twice yearly since
2008. My lab has also made important contributions to aptamer development using next generation
sequencing, and has demonstrated their exceptional efficiency to target siRNAs (1, 3) and aptamers (2, 4) to
hematopoietic cells and tumor lesions, respectively.
1. Pastor F, Kolonias D, Giangrande PH, Gilboa E. Induction of tumor immunity by targeted inhibition of
nonsense mediated mRNA decay. Nature, 2010 465:227-30
2. Pastor, F., Kolonias, D, McNamara, J., Gilboa, E., Targeting 4-1BB costimulation to disseminated tumor
lesions of mice using bi-specific oligonucleotide aptamers. Mol Ther. 2011, 19(10):1878-1886.
3. Berezhnoy, A., Castro, I., Levay, A., Malek, T.R., and Gilboa, E. Aptamer-targeted inhibition of mTOR in T
cell enhances antitumor immunity. J. Clin. Invest. 2014, 124:188-197.
4. Schrand, B., Berezhnoy, Brenneman, R., Williams, A., Levay, A., Kong, L-Y, Rao G, Zhou, S., Heimberger,
A. B., Gilboa, E. 2014. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer
conjugates enhances the therapeutic index of tumor immunotherapy, Can. Immunol. Res., 2014, 2:867-877
B. Positions and Honors
Positions and Employment
1980-1986
Assistant Professor, Department of Molecular Biology Princeton University, Princeton, NJ
1986-1993
Associate Member, Sloan Kettering Institute for Cancer Research, New York, NY
1993-2006
Professor, Departments of Surgery and Immunology & Director of Program in Immunotherapy,
Duke Center for Translational Research, Duke University Medical Center, Durham, NC
2006-present Professor, Department of Microbiology & Immunology, University of Miami Miller School of
Medicine, Miami, FL
2006-2013
Program Co-Leader,Tumor Immunobiology and Immunotherapy program, Sylvester
Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
2007-present Director, Dodson Interdisciplinary Immunotherapy Institute, University of Miami Miller School of
Medicine, Miami, FL
Other Experience and Professional Memberships (Current)
2000
Scientific Advisory Board, Yale Cancer Center
2004
External Advisory Committee, Stanford Bone Marrow Program Project
2008
External Advisory committee, Duke Brain SPORE
2010
Ad-hoc Genes & Drug Delivery NIH study section
2011
Editorial Board, OncoImmunology
2011
Editorial Board, Vaccines
2012
Editorial Board, Molecular Therapy Nucleic Acids
2013
Senior Editor, Cancer Immunology Research
2015
Chairman, ASGCT Oligonucleotide and RNAi therapeutics committee
Honors
1977-1979
1992
1993
1993-1994
2005
2006
2014
Chaim Weizmann Fellow
NIH M.E.R.I.T. Award
4th Milano Price for Gene Therapy Research
CapCURE Foundation Research Award for Gene Therapy for Prostate Cancer
Keynote speaker; International Symposium on "Recent Progress in Cell-and Gene-based
Cancer Therapy", Yonsei University, Seoul, Korea
Ruth Marshak Memorial Lecture in Cancer Immunology, Boston University
NIH NIDA Avante Garde Award
C. Contribution to Science
1. Retroviral vectors. At the start of my independent career at Princeton University (1980) I co-pioneered,
alongside Richard Mulligan and a few others, the development of retroviral vectors for gene therapy. My lab
developed the first retroviral vector that went into man, a marking study by Steve Rosenberg’s group
(Rosenberg et al. 1993, Ann. Surg. 218:455), that served as the backbone of vectors developed by Dusty
Miller’s group used in the first ADA gene therapy trials by French Anderson and Michael Blaese. My lab is
best known for the development of “self inactivating” (SIN) retroviral vectors (Yu et al., PNAS, 1986), a
safety feature that is widely used in retroviral and lentiviral vectors administered to human patients. I served
as the primary investigator or co-investigator in all of these studies.
a. Yu, S.F., T. von Ruden, P.W. Kantoff, C. Garber, M. Seiberg, U. Ruther, W.F. Anderson, E.F. Wagner, and
E. Gilboa. Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells.
Proc Natl Acad Sci U S A. 1986, 83:3194-3198
b. Kantoff, P.W., A. Gillio, J.R. McLachlin, C. Bordignon, M.A. Eglitis, N.A. Kernan, R.C. Moen, D.B. Kohn, S.F. Yu, E. Karson, S. Karlsson, J.A. Zwiebel, E. Gilboa, R.M. Blaese, A. Nienhuis, R.J. O'Reilly, and W.F.
Anderson. Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated
gene transfer. J. Exp. Med., 1987, 166:219-234
c. Hantzopoulos, P.A., B.A. Sullenger, G. Ungers, and E. Gilboa. Improved gene expression upon transfer of
the adenosine deaminase minigene outside the transcriptional unit of a retroviral vector. Proc Natl Acad Sci
U S A., 1989, 86:3519-3523.
2. HIV/AIDS gene therapy. After moving to Memorial Sloan Kettering Cancer Center (MSKCC) in New York
City (1986) I expanded my research interest to HIV/AIDS, focusing on the development of ways to render
human CD4+ T cells genetically resistant to HIV infection dubbed “intracellular immunization”. To this end, I
described a novel approach of stably expressing retrovirally-encoded short ribooligonucleotide “TAR
decoys” in human CD4+ T cells (Sullenger et al., Cell, 1990), which are currently tested in HIV-infected
patients (Di-Giusto, Sci. Transl. Med. 2010, 2:36ra43). As a precursor to this approach, my laboratory was
the first to use pol III promoters to express short RNA molecules in the cells (Sullenger, Mol. Cell Biol.,
1990), specifically TAR decoys, that became the method of choice for expressing shRNAs and microRNAs
in cells. I served as the primary investigator in all of these studies.
a. Sullenger, B.A., T.C. Lee, C.A. Smith, G.E. Ungers, and E. Gilboa. Expression of chimeric tRNA-driven
antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication.
Mol Cell Biol., 1990, 10:6512-6523.
b. Sullenger, B.A., H.F. Gallardo, G.E. Ungers, and E. Gilboa. Overexpression of TAR sequences renders
cells resistant to human immunodeficiency virus replication. Cell, 1990, 63:601-608
c. Lee, T.C., B.A. Sullenger, H.F. Gallardo, G.E. Ungers, and E. Gilboa. Overexpression of RRE-derived
sequences inhibits HIV-1 replication in CEM cells. New Biol., 1992, 4:66-74
3. Cancer vaccines. Given the cancer focus at MSKCC I developed a program in cancer immunotherapy, copioneering, alongside Glenn Dranoff and other investigators, the development of gene-modified autologous
tumor vaccines (Connor et al., J. Exp. Med., 1993). A chance encounter with the late Ralph Steinman at the
neighboring Rockefeller University I became interested in developing dendritic cell (DC)-based cancer
vaccines. During my subsequent tenure at Duke University we developed a novel approach to load DC with
tumor antigens by transfection with the corresponding mRNA, a counterintuitive idea that met with health
skepticism (Boczkowski et al., J. Exp. Med., 1996) . Nonetheless, mRNA transfection of DC became the
method of choice in DC vaccine clinical trial in cancer patients by us and by other groups. Using mRNA
transfected DC we have shown that telomerase can be used as a “universal” antigen (Nair et al, Nat. Med.,
2000) and that tumor stroma products that are not expressed in the transformed tumor cells can function as
effective tumor rejection antigens (Lee et al., Can. Res., 2005). I served as the primary investigator in all of
these studies.
a. Connor, J., R. Bannerji, S. Saito, W. Heston, W. Fair, and E. Gilboa. Regression of bladder tumors in mice
treated with interleukin 2 gene- modified tumor cells, J Exp Med., 1993, 177:1127-1134
b. Nair, S.K., D. Boczkowski, M. Morse, R.I. Cumming, H.K. Lyerly, and E. Gilboa. Induction of primary
carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells
transfected with RNA. Nat Biotechnol., 1998, 16:364-369.
c. Nair, S.K., A. Heiser, D. Boczkowski, A. Majumdar, M. Naoe, J.S. Lebkowski, J. Viweg, and E. Gilboa.
Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase
reverse transcriptase RNA transfected dendritic cells. Nature Medicine, 2000, 6:1011-1017
d. Lee, J., M. Fassnacht, S. Nair, D. Boczkowski and E. Gilboa. Tumor immunotherapy targeting fibroblast
activation protein (FAP), a product expressed in tumor-associated fibroblasts. Can. Res., 2005, 65:1115611163.
4. Aptamer targeted immune modulation. The goal of our current program is to develop a combination of
clinically feasible and broadly applicable treatments to increase the susceptibility of disseminated tumor
lesions to immune elimination. Addressing a main challenge in clinical oncology, dose limiting drug toxicity,
we are developing oligonucleotide-based immune modulatory agents that are targeted to the tumor or the
immune system by conjugation to an oligonucleotide aptamer ligand. The chemically synthesized aptamer
ligands represents a potentially superior alternative to monoclonal antibodies in term of development, cost of
manufacture, and regulatory approval process. Using aptamer-targeted siRNA conjugates we have
developed new concepts in cancer immunotherapy, to enhance the antigenicity of disseminated tumor
lesions (Pastor et al., Nature, 2010), to potentiate immune memory (Berezhnoy et al., J. Clin. Invest., 2014),
and used heterobispecific aptamers to target costimulation to the tumor site (Schrand et al., Can. Immunol.
Res., 2014). In preclinical murine tumor models the aptamer targeted strategies were superior to
corresponding “gold standard” antibody or drug based therapies, and exhibited significantly reduced toxicity.
Emphasis is now shifting to clinical trials in cancer patients. Given that isolation of high affinity aptamer has
been a challenging task, our lab is developing next generation sequencing-guided selection procedures that
enhance the feasibility and reduce the uncertainty of isolating high affinity aptamer ligands (Berezhnoy et al.,
2012). I served as the primary investigator in all of these studies.
a. Pastor F, Kolonias D, Giangrande PH, Gilboa E. Induction of tumor immunity by targeted inhibition of
nonsense mediated mRNA decay. Nature, 2010 465:227-30
b. Berezhnoy, A, Stewart, C. A., James McNamara, J., Thiel, W., Giangrande, P., Giorgio Trinchieri, G., and
Gilboa, E. Isolation & optimization of murine IL-10 receptor blocking oligonucleotide aptamers using highthroughput sequencing. Mol. Ther., 2012, 20:1242.
c. Berezhnoy, A., Castro, I., Levay, A., Malek, T.R., and Gilboa, E. Aptamer-targeted inhibition of mTOR in T
cell enhances antitumor immunity. J. Clin. Invest. 2014, 124:188-197.
d. Schrand, B., Berezhnoy, Brenneman, R., Williams, A., Levay, A., Kong, L-Y, Rao G, Zhou, S., Heimberger,
A. B., Gilboa, E. 2014. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer
conjugates enhances the therapeutic index of tumor immunotherapy, Can. Immunol. Res., 2014, 2:867-877
List of published work in PubMed: http://www.ncbi.nlm.nih.gov/pubmed/?term=eli+gilboa (from 2002);
http://www.ncbi.nlm.nih.gov/pubmed?term=Gilboa+E&cmd=DetailsSearch (all)
D. Research Support
Ongoing Research Support
R01CA181598
Gilboa (PI)
07/15/14-07/14/19
Enhancing immunological memory using aptamer targeted siRNA delivery to T cells.
The proposed studies are designed to enhance the persistence of vaccine-induced immune response by
aptamer-targeted siRNA inhibition of effector mediators in CD8+ T cells.
Role: PI
PC130382
Gilboa (PI)
05/01/14-04/30/17
Potentiating Tumor Immunity in the Murine TRAMP Model for Prostate Cancer Using Aptamer-Targeted RNAi
To Render CD8+T Cells Resistant to TGFbeta Inhibition.
The proposed studies is to develop aptamer-targeted siRNA conjugates to render vaccine-induced T cells
resistant to TGFb inhibition in models for prostate cancer.
Role: PI
BC130871
Gilboa(PI)
04/01/14-03/31/17
Enhancing Therapeutic Index by Targeting Costimulation to the Tumor Stroma with Bispecific Oligonucleotide
Aptamers
The proposed studies are to develop VEGF-4-1BB aptamer conjugates to promote tumor-specific costimulation
of vaccine activated T cells in models of breast cancer.
Role: PI
1DP1DA039560-01 (Gilboa)
03/1/15-02/28/19
NIH/NIDA
Reversing HIV T cell dysfunction by aptamer targeting of therapeutic siRNAs
The proposed studies to develop a broadly applicable clinically feasible approach to target intracellular
mediators of immune exhaustion that integrate signals from multiple inhibitory receptors. Studies will be carried
out using in vitro cultured T cells obtained from HIV-infected patients.
Role: PI
Completed Research Support (past 3 years)
1R01CA151857 Gilboa (PI)
04/01/11-02/29/16
Expressing new tumor antigens by inhibition of nonsense mediated mRNA decay.
The proposed studies are to enhance the antigenicity of tumor cells by using aptamer-siRNA conjugates to
inhibit the nonsense mediated mRNA decay process in prostate tumor cells
Role: PI
KG100038
Gilboa (PI)
06/01/10-05/31/13
Susan Komen
Potentiating Tumor Immunity in Breast Cancer Patients using Aptamer-Targeted Foxp3 siRNA to Inactivate
Regulatory T Cells
The studies proposed in this grant application will develop a tumor targeted approach to inactivate regulatory T
cells by using nucleic acid based aptamers as targeting ligands to delivery foxp3 siRNA to regulatory T cells.
Role: PI
KG090348
Gilboa (PI)
04/01/09-03/31/12
Development of Agonistic 4-1BB Aptamers to Enhance Vaccine-Induced Tumor Immunity
The studies proposed in this grant application will develop nucleic acid based immune modulatory reagents to
promote tumor costimulation.
Role: PI