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Masoud H. Manjili ,
D.V. M., Ph.D.
Assistant Professor

Phone: (804) 828-8779
Dept. Fax: (804) 828-8453
e-mail:
mmanjili@vcu.edu
Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
Massey Cancer Center Goodwin Research Laboratory Room 286
PO Box 980035
401 College Street
Richmond, VA 23298-0035
Professional Experience
- D.V.M.,
1990, University of Tehran
- Ph.D.,
1996, University of Sydney
- Research
Scientist, 1997-1999, Razi Vaccine & Serum Institute, Pasteur Institute
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Postdoctoral, 1999-2002, Roswell Park Cancer Institute
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Instructor, 2003-2004, Roswell Park Cancer Institute, State University
of New York at Buffalo
Research Interests:
Mechanisms of tumor escape/recurrence and antigen loss.
While immune responses are induced against variety of cancers resulting in
the inhibition of tumor development, molecular alterations in tumors can
occur under immune pressure resulting in the tumor escape. In other words,
anti-tumor immune responses can function as a “double-edged” sword exerting
both host-protective and tumor-sculpting effects on developing tumors. Such
tumor immunoediting process could induce epigenetic changes in tumors
resulting in tumor antigen loss and
recurrence of primary or metastatic tumors. Therefore, one of the challenges
in the immunotherapy of cancers is how to prevent tumor escape. Using HER-2/neu
over-expressing breast carcinoma and its relapsed HER-2/neu antigen negative
variant, we seek to identify the immunological components that are involved
in tumor escape/relapse as well as those involved in tumor rejection. We
have identified IFN-gamma as one of the cytokines involved in downregulation
of HER-2/neu and subsequent tumor escape.
Understanding the mechanisms of
tumor-specific immune suppression by myeloid-derived suppressor cells (MDSC)
and developing strategies to overcome such immune suppression.
Development of
mammary tumors coincides with elevated Gr1+CD11b+ myeloid-derived suppressor
cells (MDSC). Tumor-derived soluble factors, inflammatory cytokines in
particular, are likely involved in the generation of these suppressor cells.
Failure of anti-tumor immune responses to eradicate well-established solid
tumors is because of the abundance of tumor-derived factors that increases
MDCS. Therefore, well-established solid tumors are more resistant to
immunotherapy compared to residual tumors. We seek to develop strategies to
inhibit elevation of MDSC by using anti-inflammatory compounds and identify
tumor-derived factors that facilitate recruitment of MDSC from bone marrow,
with a goal to improve immunotherapy of breast carcinomas.
Identification
of immunogeneic epitopes of HER-2/neu and novel antigenic targets that are
involved in tumor rejection and recurrence-free survival using heat shock
protein-based vaccines.
Taking advantage of these
important properties of heat shock proteins (HSPs) to induce both innate and
adaptive immune responses, we generated chaperone-based recombinant cancer
vaccines targeting breast tumor antigens, HER-2/neu, for immunotherapy of
cancers. HSP110-HER-2/neu chaperone vaccine was capable of inducing HER-2/neu
specific anti-tumor immune responses against HER-2/neu over-expressing
breast tumors resulting in tumor inhibition in animal models. However,
HER-2/neu antigen loss under immune pressure resulted in tumor recurrence.
We seek to identify novel antigenic targets for development of more
effective HSP-based cancer vaccines. We have identified several potential
antigenic targets that remain intact after HER-2/neu antigen loss. We are
also identifying certain epitopes and domains of HER-2/neu that may have
potential for the induction of effective anti-tumor immune responses and
reducing tumor recurrence.
Selected Publications:
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Morales JK, Kmieciak M, Graham L, Feldmesser M, Bear HD, Manjili MH.
Adoptive transfer of HER2/neu specific T cells expanded with alternating
gamma chain cytokines mediate tumor regression when combined with the
depletion of myeloid-derived suppressor cells. Cancer Immunol
Immunother (In press), 2008
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Habibi M, Kmieciak M, Graham L, Morales JK, Bear HD, Manjili MH.
Radiofrequency thermal ablation of breast tumors combined with
intralesional administration of IL-7 and IL-15 augments anti-tumor
immune responses and inhibits tumor development and metastasis.
Breast Cancer Res Treat. (In press), 2008
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Manjili MH
and Kmieciak M.
Immunotherapy of cancer using
heat shock protein vaccines: A retreat from bedside to bench. In F.
Columbus (Eds. Emma Morel and Camille Vincent), Heat shock proteins: new
research, 1st edition, pp. 89-110. New York, NY: Nova Science
Publishers, Inc. 2008
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Manjili MH, Kmieciak M. Does HER-2/neu
antigen loss in metastatic breast cancer occur under immune pressure?
Int J Cancer 123(6):1476-7,
2008
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Ghadersohi A, Odunsi k, Zhang s, Azrak RG, Bundy BN, Manjili MH,
Li F. Prostate-derived
Ets
transcription factor (PDEF) as a favorable prognostic marker in ovarian
cancer patients. Int J Cancer
123(6):1376-84,
2008
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Worschech A, Kmieciak M, Knutson KL, Bear HD, Szalay AA, Wang E,
Marincola FM, Manjili MH. Signatures associated with rejection or
recurrence in HER-2/neu positive mammary tumors.
Cancer Res
68(7):2436—46, 2008
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Kmieciak M, Morales JK, Morales J, Bolesta E, Grimes M, Manjili MH.
Danger signal and nonself
entity of tumor antigen are both required for eliciting effective immune
responses against HER-2/neu positive mammary carcinoma: implications for
vaccine design. Cancer Immunol Immunother 57(9):1391-8,
2008
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Reiman JM, Kmieciak M, Manjili MH, Knutson KL. Tumor
immunoediting and immunosculpting: pathways to immune escape and disease
progression. Semin Cancer Biol 17(4):275-87,
2007
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Kmieciak M, Knutson KL, Dumur C, Manjili MH.
HER-2/neu antigen loss and relapse of mammary
carcinoma are actively induced by T cell-mediated anti-tumor immune
responses. Eur J Immunol.
37:675-85, 2007
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Manjili MH. Come
forth 1E10 anti-idiotype vaccine: delivering the promise to
immunotherapy of small cell lung cancer. Cancer Biol Ther
6:151-152, 2007
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Segal BH, Wang X-Y, Carly GD, Youn R, Repasky EA, Manjili MH,
Subjeck JR. Heat shock proteins as vaccine adjuvants in infections and
cancer. Drug Discov Today 11:534-40, 2006
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Manjili MH, Arnouk H, Knutson KL,
Kmieciak M, Disis ML, Subjeck JR, Kazim AL. Emergence of immune escape
variant of mammary tumors that has distinct proteomic profile and a
reduced ability to induce “danger signals”. Breast Cancer Res Treat
96:233-41, 2006
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Manjili MH, Park J, Facciponte JG, Wang
X-Y, Subjeck JR. Immunoadjuvant chaperone, GRP170, induces “danger
signals” upon interaction with dendritic cells. Immunol and Cell Biol
84: 203-8, 2006
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Park J, Facciponte JG, Chen X, MacDonald I, Repasky EA, Manjili MH,
Wang X-Y, Subjeck JR. Chaperoning function of stress protein grp170, a
member of the hsp70 superfamily, is responsible for its immunoadjuvant
activity. Cancer Res 66:1161-8, 2006
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Manjili MH, Kmieciak M, Keeler J. Comment
on “Tumor progression can occur despite the induction of very high
levels of self/tumor antigen-specific CD8+ T cells in patients with
melanoma”. J Immunol 176:4511, 2006
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Facciponte JG, MacDonald I, Wang X-Y, Park JE, Arnouk H, Grimm MJ, Li Y,
Kim H, Manjili MH, Easton DP, Subjeck JR. Heat shock proteins
HSP70 and GP96: structural insights. Cancer Immunol Immunother
255:339-46, 2006
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Zhao YL, Murthy SN,
Manjili MH, Guan LJ, Sen A, Hui SW. Induction of cytotoxic T
lymphocytes by electroporation enhanced needle-free skin immunization.
Vaccine 24(9):1282-9, 2006
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Facciponte JG,
MacDonald I, Wang X-Y, Kim H, Manjili MH, Subjeck JR. Heat shock
proteins and scavenger receptors: role in adaptive immune responses.
Immunol Invest 34: 325-342, 2005
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Manjili MH,
Park J, Facciponte JG, Subjeck JR. HSP110 induces “danger signals” upon
interaction with antigen presenting cells and mouse mammary carcinoma.
Immunobiology 210: 295-303, 2005
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Manjili MH,
Wang X-Y, Macdonald IJ, Arnouk H, Yang GY, Pritchard MT, Subjeck JR.
Cancer Immunotherapy and Heat Shock Proteins: promises and challenges.
Expert Opin Biol Ther 4(3): 363-373, 2004
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Wang X-Y,
Manjili MH, Park J, Chen X, Repasky E, Subjeck JR. Development of
cancer vaccines using autologous and recombinant high molecular weight
stress proteins. Methods 32:13-20, 2004
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Manjili MH,
Wang X-Y, Chen X, Martin T, Repasky EA, Henderson R, Subjeck JR.
HSP110-HER-2/neu chaperone complex vaccine induces protective immunity
against spontaneous mammary tumors in HER-2/neu transgenic mice. J
Immunol 171:4054-4061, 2003
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Wang X-Y, Chen X,
Manjili MH, Repasky EA, Henderson R, Subjeck JR. Targeted
immunotherapy using in vitro reconstituted chaperon complex of HSP110
and melanoma associated antigen gp100. Cancer Res 63:2553-2560,
2003
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Manjili MH,
Wang X-Y, Park J, MacDonald I., Li Y, van Schie R, Subjeck JR. Cancer
immunotherapy: stress proteins and hyperthermia. Int J Hyperthermia
18: 506-521, 2002
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Wang X-Y, Li Y,
Manjili MH, Repasky EA, Pardoll DM, Subjeck JR. HSP110
overexpression increases the immunogenicity of the murine CT26 colon
tumor. Cancer Immunol Immunother 51: 311-319, 2002
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Manjili MH,
Henderson R, Wang X-Y, Repasky E, Kazim L, Subjeck JR. Development of a
recombinant HSP110-HER-2/neu vaccine using the chaperoning properties of
HSP110. Cancer Res 62: 1737-1742, 2002
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Manjili MH,
Wang X-Y, Park J, Facciponte J, Subjeck JR. Immunotherapy of cancer
using heat shock proteins. Front Biosci 7: 43-52, 2002
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Manjili MH,
Sangster NC, Rothwell TLW. In vitro leucocyte proliferative responses
and lymphocyte sub-types in guinea pigs with genetically determined
high- and low-level responsiveness to Trichostrongylus colubriformis.
Parasitol Res 86: 311-317, 2000
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Manjili MH,
Sangster NC, Rothwell TLW. Antibody production in guinea pigs with
genetically-determined high and low responsiveness to Trichostrongylus
colubriformis. Int J Parasitol 29: 225-261, 1999
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Manjili MH,
France MP, Sangster NC, Rothwell TLW. Quantitative and qualitative
changes in intestinal goblet cells during primary infection of
Trichostrongylus colubriformis high and low responder guinea pigs.
Int J Parasitol 28: 761-765, 1998
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