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
• Postdoctoral, 1999-2002, Roswell Park Cancer Institute
• 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:

1. 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
2. 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
3. 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, 1^st edition, pp. 89-110. New York, NY: Nova Science Publishers, Inc. 2008
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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
27. Manjili MH, Wang X-Y, Park J, Facciponte J, Subjeck JR. Immunotherapy of cancer using heat shock proteins.  Front  Biosci 7: 43-52, 2002
28. 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
29. 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
30. 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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