Jianlin Gong, MD
PI Name: Jianlin Gong, MD
Research Interests: Development of tumor vaccine and cancer immunotherapy.
Clinical Interests: Breast and ovarian cancers.
Research Summary: My laboratory works in the translational research of cancer therapy. We have focused on the development of dendritic cells (DC)-based vaccine, chaperone protein-based vaccine and combined therapy in the treatment of cancer.
DC-based tumor vaccine
Dendritic cells are the most potent antigen presenting cells in the body, whereas tumor cells express abundant tumor antigens. The fusion of DC and tumor cells represents an attractive approach to deliver, process and subsequently present tumor antigen to the immune system. Immunization of mice with DC-tumor fusion vaccine eliminated established pulmonary metastases. Co-culture of cancer patient-derived T cells with the fusion vaccine induced CTL against autologous tumor cells. Thus the fusion cell technology has been widely used in the production of DC-based tumor vaccines.
Chaperone protein-based tumor vaccine
Heat shock proteins (Hsps) are members of a number of families of stress-inducible proteins whose main intracellular functions are as molecular chaperones. In addition, Hsps are also powerful agents in immunotherapy. When Hsp-peptide complexes are extracted and used as a tumor vaccine, it can mediate malignant cell killing in a specific manner by cytotoxic CD8++T cells and lead to tumor regression. However, it is becoming apparent that heat shock protein complexes purified from tumor cells have limited effectiveness as tumor vaccines. Therefore, we extracted Hsps from DC-tumor fusion cells and used as a tumor vaccine. Hsp70-peptide complexes (Hsp70.PC) derived from DC-tumor fusion cells possess superior properties such as stimulation of DC maturation and T cell proliferation over its counterpart from tumor cells. More importantly, immunization of mice with Hsp70.PC-F resulted in a T-cell-mediated immune response that was able to provide protection of mice against challenge with tumor cells. These results indicate that Hsp70.PC-F constitute an improved formulation of chaperone protein-based tumor vaccine.
Combined therapy for cancer
Although tumor vaccines mentioned above are effective in the animal models, their effect as a single therapy is limited since majority of patients treated with these vaccines are in the advanced stage of disease. It is apparent that immunotherapy alone is insufficient to treat advanced stage of tumors. Therefore, we aim to develop a combined therapy. We recently collaborate with radiation oncologist to develop combined radiotherapy and immunotherapy for the treatment of advanced stage of breast cancer. In addition, we also found that patient-derived ovarian cancer cells expressing stem cell markers are more resistant to chemotherapy. We therefore aim to develop a vaccine targeting ovarian cancer cells expressing stem cell markers.
Desheng Weng, MD, PhD. email: email@example.com
Baizheng Song, DMD. email: firstname.lastname@example.org
Zhengrong Wu, MD, PhD. email: email@example.com
Gong J, Avigan D., Chen DS, Wu ZK, Koido S, Kashiwaba M and Kufe D. Activation of Antitumor Cytotoxic T Lymphocytes by Fusions of Human Dendritic Cells and Breast Carcinoma Cells. Proc. Natl. Acad. Sci. USA. 2000, 97(6):2715-2718.
Chen DS, Koido S, Li Y, Gendler S, and Gong J. T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice. Breast Cancer Research and Treatment 2000,16(2):107-115.
Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D.,and Kufe D. Fusions of Human Ovarian Carcinoma Cells with Autologous and Allogeneic Dendritic Cells Induce Anti-Tumor Immunity. J. Immunol. 2000, 165:1705-1711.
Gong J, Apostolopoulos V, Chen DS, Koido S, Rowse G, Gendler S, McKenzie IF and Kufe DW. Selection and Characterization of MUC1-Specific CD8+ T cells from MUC1 Transgenic Mice immunized with Dendritic-Carcinoma Fusion Cells. Immunology, 2000, 101:316-324.
Koido, S., Chen, D., Gendler, SJ. Kufe, D. and Gong J. Induction of Antitumor Immunization Using Bone Marrow-Generated Dendritic Cells Transfected With MUC1 RNA. J Immunol., 2000, 165:5713-5719.
Homma S, Toda G, Gong J, Kufe D, Ohno T. Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice. J Gastroenterol., 2001, 36:764-771.
Tanaka Y, Koido S, Chen D, Gendler S, Kufe D and Gong J. Vaccination with Allogeneic Dendritic Cells Fused to Carcinoma Cells Induces Antitumor Immunity in MUC1 Transgenic Mice. Clini. Immuno., 2001, 101:192-200.
Gong J, Koido S, Chen D, Tanaka Y, Huang L, Avigan D, Anderson K, Ohno T, Kufe D. Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood, 2002, 99:2512-2517.
Koido S, Tanaka Y, Chen D, Kufe D and Gong J. The kinetics of in-vivo priming of CD4 and CD8 T cells by dendritic/tumor fusion cells in MUC1 transgenic mice. J. Immuno., 2002, 168:2111-2117.
Xia J, Tanaka Y, Koido S, Liu Mukherjee P, Gendler S and Gong J. Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells. J. Immuno., 2003, 170:1980-1986.
Chen D, Xia J, Tanaka Y, Chen H, Koido S, Oliver W, Mukherjee P, Gendler S, Kufe D and Gong J. Immunotherapy of spontaneous mammary carcinoma with fusion of dendritic cells and mucin 1-positive carcinoma cells. Immunology, 2003, 109:300-307.
Gong J, Koido S, Kato Y, Tanaka Y, Chen D, Jonas A, Galinsky I, DeAngelo D, Avigan D, Kufe D and Stone R. Induction of Anti-leukemic Cytotoxic T Lymphocytes by Fusion of Patient-derived Dendritic Cells with Autologous Myeloblasts. Leu. Res., 2004, 28:1303-1312.
Avigan D, Borges V, Gong J, Wu Z, Uhl L, Smith T, Giallambardo N, Schadt K, Tetreault JC and Kufe D. Fusion Cell Vaccination of Patients with Metastatic Breast Cancer Induces Immunologic and Clinical Responses. Clin. Cancer Res., 2004, 10:4699-4708.
Koido S, Xia J, Tanaka Y, Ohana M, Liu C, Gong J. Dendritic cells fused with human cancer cells: morphology, antigen presentation and T-Cell stimulation. Clin. Immunol. 2004, 113:261-269.
Tanaka Y, Koido S, Xia JC, Ohana M, Liu C, Cote G, Sawyer D, Calderwood S and Gong J. Development of Antigen-Specific CD8+ Cytotoxic T Lymphocytes in MHC Class I-Deficient Mice through CD4 to CD8 Conversion. J Immunol., 2004, 172:7848-7858.
Koido S, Nikrui N, Ohana M, Xia J, Tanaka Y, Liu C, Durfee JK, Lerner A and Gong J. Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use. Gynecol Oncol. 2005, 99:462-471.
Tanaka Y, Koido S, Ohana M, Liu C, Gong J. Impaired antitumor immunity induced by fusions of MHC class II-deficient dendritic cells with tumor cells. J Immunol., 2005, 174:1274-1280.
Khaleque A, Bharti A, sawyer D, Gong J, Benjamin I, Stevenson MA, Calderwood SK. Induction of heat shock proteins by heregulin 1 leads to protection from apoptosis and anchorage independent growth. Oncogene 2005, 24:6564-6573.
Calderwood SK, Theriault J, Gong J. Message in a Bottle: Role of the 70 kilodalton heat shock protein family in anti-tumor immunity. Eur. J Immunol 2005, 35:2518-2527.
Koido S, Hara E, Homma S, Torii A, Toyama Y, Kawahara H, Watanabe M, Yanaga K, Fujise K, Tajiri H, Gong J and Toda G. Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells. Clin. Cancer Res., 2005, 11:7891-7900.
Calderwood SK, Theriault J, Gong J. How is the immune response affected by hyperthermia and heat shork proteins? Int. J. Hyperthermia, 2005, 21:713-716.
Enomoto Y, Bharti A, Khaleque A, Song BZ, Liu C, Apostolopoulos V, Xing P, Calderwood SK and Gong J. Enhanced immunogenicity of HSP70 peptide complexes from DC-tumor fusion cells. J Immunol., 2006, 177:5946-5955.
Gong J. Immunotherapy of cancer based on DC–tumor fusion vaccine. Current Immunol Rew., 2006, 2:291-304.
Koido S, Tanaka Y, Tajiri H and Gong J. Generation and functional assessment of antigen-specific T cells stimulated by Fusions of Dendritic Cells and allogeneic breast cancer cells. Vaccine, 2007, 25:2610-2619.
Calderwood SK, Theriault J, Gray PJ, Gong J. Cell surface receptors for molecular chaperones. Methods, 2007, 43:199-206.
Gong J, Koido S, Calderwood SK. Cell fusion: from hybridoma to dendritic cell-based vaccine. Expert Rev Vaccines. 2008, 7:1055-1068.
Khaleque A, Bharti A, Gong J, Gray PJ, Sachde V, Ciocca DR, Stati A, Fanelli M, Calderwood SK. Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1. Oncogene, 2008, 20:1886-93.
Gong J, Zhu BZ, Murshid A, Adachi H, Song BZ, Lee A, Calderwoord SK. (2009) T cell activation by HSP70 vaccine requires TLR signaling and scavenger receptor SREC-1. J Immunol., 183:3092-3098.
Jaskelioff M, Song W, Xia J, Liu C, Kramer J, Koido S, Gendler S, Calderwood SK and Gong J. Telomerase deficiency and telomere dysfunction inhibit mammary tumors induced by polyomavirus middle T oncogene. Oncogene, 2009, 28:4225-4236.
Gong J, Zhang YF, Durfee J, Weng DS, Liu C, Koido S, Song BZ, Apostolopoulos V and Calderwood S. An HSP70-based vaccine with enhanced immunogenicity for clinical use. J Immunol., 2010, 184:488-496.
Murshid A, Gong J and Calderwood SK. Heat Shock Protein 90 Mediates Efficient Antigen Cross Presentation through the Scavenger Receptor Expressed by Endothelial Cells-I. J Immunol., 2010, 185:2903-2917.
Weng D, Cunin MC, Song B, Price BD, Eller MS, Gilchrest BA, Calderwood SK, Gong J. Radiosensitization of mammary carcinoma cells by telomere homolog oligonucleotide pretreatment. Breast Cancer Res. 2010 (in press)