Christine Brown, Ph.D.
Christine Brown, Ph.D., is a faculty member in the departments of Hematology & Hematopoietic Cell Transplantation and Immuno-Oncology.
As deputy director of the T Cell Therapeutics Research Laboratory, Dr. Brown, The Heritage Provider Network Professor in Immunotherapy, provides scientific oversight for the preclinical research program, as well as the ongoing clinical trial program focused on the development of CAR-engineered T cells for the treatment of hematological malignancies and solid tumors. Dr. Brown’s personal research efforts are focused on developing and refining redirected CAR T cells for the treatment of malignant brain tumors.
Dr. Brown received her doctoral degree from University of California Berkeley, and was a Leukemia & Lymphoma Scholar during her postdoctoral fellowship at Pennsylvania State University. Her scientific contributions to the development and optimization of tumor-specific CAR T cells for the treatment of glioblastoma are supported by the California Institute for Regenerative Medicine and are the basis of an ongoing phase I clinical trial which is supported by Gateway for Cancer Research and R01 FD005129.
Location
Duarte Cancer Center
Duarte, CA 91010
Education & Experience
1992-1998, Ph.D., Department of Cell and Molecular Biology, University of California Berkeley, Berkeley, CA
1985-1990, Bachelor of Science, Combined Science - emphasis Biochemistry, minor Chemistry, Santa Clara University, Santa Clara, CA
1998-2001, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA
2016-present, The Heritage Provider Network Professor in Immunotherapy, City of Hope, Duarte, CA
2019-present, Deputy Director, T Cell Therapeutics Research Laboratory, City of Hope, Duarte, CA
2013-2019, Associate Director, T Cell Therapeutics Research Laboratory, City of Hope, Duarte, CA
2010-present, Professor, Departments of Hematology & Hematopoietic Cell Transplantation and Immuno-Oncology, City of Hope, Duarte, CA
2005-2013, Group Leader, T cell Therapy Preclinical Research, Department of Cancer Immunotherapeutics & Tumor Immunology, Beckman Research Institute of City of Hope, Duarte, CA
2002-2010, Assistant Research Professor, Department of Cancer Immunotherapeutics & Tumor Immunology, Beckman Research Institute of City of Hope, Duarte, CA
Research
My research is focused on the development of chimeric antigen receptor (CAR) T cell therapy for the treatment of cancer. I conceptualize, perform and oversee studies to evaluate CAR design, T cell manufacturing, cell-based immunological assays and in vivo animal models. My primary independent research efforts are focused on the development of CAR T cell therapy for the treatment of primary and metastatic brain tumors.
As deputy director of the T Cell Therapeutics Research Laboratory, I also lead multifunctional teams to translate these therapies to the clinical, participating in all stages of the regulatory process.
Awards & Memberships
Awards
1998, Postdoctoral Fellowship, Howard Hughes Medical Institute
2000, Scholar, Leukemia and Lymphoma Society
2012, Values in Action Award for Intellectual Curiosity, City of Hope
2013, Developmental Research Award Recipient, Lymphoma SPORE
Memberships
American Association for Cancer Research
American Society of Gene and Cell Therapy
Society of Immunotherapy of Cancer
Society of Neuro-Oncology
Caltech/UCLA/CHLA/COH Engineered Immunity Consortium
Publications
Information listed here is obtained from Pubmed, a public database; City of Hope is not responsible for its accuracy. View all publications.
- Cui Q, Yang S, Ye P, Tian E, Sun G, et al. Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis. Nature communications. 2016; 7:10637. PubMed [journal] PMID: 26838672, PMCID:PMC4742843
- Hong H, Brown CE, Ostberg JR, Priceman SJ, Chang WC, et al. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice. PloS one. 2016; 11(1):e0146885. PubMed [journal] PMID: 26761817, PMCID: PMC4711972
- Priceman SJ, Forman SJ, Brown CE. Smart CARs engineered for cancer immunotherapy. Current opinion in oncology. 2015; 27(6):466-74. NIHMSID: NIHMS733405 PubMed [journal] PMID: 26352543, PMCID: PMC4659816
- Brown CE, Badie B, Barish ME, Weng L, Ostberg JR, et al. Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015; 21(18):4062-72. NIHMSID: NIHMS699687 PubMed [journal] PMID: 26059190, PMCID: PMC4632968
- Wang X, Wong CW, Urak R, Mardiros A, Budde LE, et al. CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015; 21(13):2993-3002. NIHMSID: NIHMS677258 PubMed [journal] PMID: 25838392, PMCID: PMC4489991
- Jonnalagadda M, Mardiros A, Urak R, Wang X, Hoffman LJ, et al. Chimeric antigen receptors with mutated IgG4 Fc spacer avoid fc receptor binding and improve T cell persistence and antitumor efficacy. Molecular therapy : the journal of the American Society of Gene Therapy. 2015; 23(4):757-68. PubMed [journal] PMID: 25366031, PMCID: PMC4395772
- Wen W, Liang W, Wu J, Kowolik CM, Buettner R, et al. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer. Molecular cancer therapeutics. 2014; 13(12):3037-48. NIHMSID: NIHMS634418 PubMed [journal] PMID: 25319391, PMCID: PMC4321961
- Thaci B, Brown CE, Binello E, Werbaneth K, Sampath P, et al. Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy. Neuro-oncology. 2014; 16(10):1304-12. PubMed [journal] PMID: 24723564, PMCID: PMC4165413
- Herrmann A, Cherryholmes G, Schroeder A, Phallen J, Alizadeh D, et al. TLR9 is critical for glioma stem cell maintenance and targeting. Cancer research. 2014; 74(18):5218-28. NIHMSID: NIHMS614918 PubMed [journal] PMID: 25047528, PMCID: PMC4167470
- Hong H, Stastny M, Brown C, Chang WC, Ostberg JR, et al. Diverse solid tumors expressing a restricted epitope of L1-CAM can be targeted by chimeric antigen receptor redirected T lymphocytes. Journal of immunotherapy (Hagerstown, Md. : 1997). 2014; 37(2):93-104. PubMed [journal] PMID: 24509172
- Wang D, Starr R, Chang WC, Aguilar B, Alizadeh D, Wright SL, Yang X, Brito A, Sarkissian A, Ostberg JR, Li L, Shi Y, Gutova M, Aboody K, Badie B, Forman SJ, Barish ME, Brown CE. Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci Transl Med. 2020 Mar 4;12(533). DOI: 10.1126/scitranslmed.aaw2672. PubMed PMID: 32132216.
- Alizadeh D, Wong RA, Yang X, Wang D, Pecoraro JR, Kuo CF, Aguilar B, Qi Y, Ann DK, Starr R, Urak R, Wang X, Forman SJ, Brown CE. IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype. Cancer Immunol Res. 2019 May;7(5):759-772. DOI: 10.1158/2326-6066.CIR-18-0466. Epub 2019 Mar 19. PubMed PMID: 30890531; PubMed Central PMCID: PMC6687561.
- Wang D, Aguilar B, Starr R, Alizadeh D, Brito A, Sarkissian A, Ostberg JR, Forman SJ, Brown CE. Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. JCI Insight. 2018 May 17;3(10). DOI: 10.1172/jci.insight.99048. eCollection 2018 May 17. PubMed PMID: 29769444; PubMed Central PMCID: PMC6012522.
- Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D'Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016 Dec 29;375(26):2561-9. DOI: 10.1056/NEJMoa1610497. PubMed PMID: 28029927; PubMed Central PMCID: PMC5390684.
- Priceman SJ, Tilakawardane D, Jeang B, Aguilar B, Murad JP, Park AK, Chang WC, Ostberg JR, Neman J, Jandial R, Portnow J, Forman SJ, Brown CE. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain. Clin Cancer Res. 2018 Jan 1;24(1):95-105. DOI: 10.1158/1078-0432.CCR-17-2041. Epub 2017 Oct 23. PubMed PMID: 29061641; NIHMSID:NIHMS1619325.
Lab Research Manuscripts
- Sahoo P, Yang X, Abler D, Maestrini D, Adhikarla V, Frankhouser D, Cho H, Machuca V, Wang D, Barish M, Gutova M, Branciamore S, Brown CE, Rockne RC. Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data. J R Soc Interface. 2020 Jan;17(162):20190734. DOI: 10.1098/rsif.2019.0734. Epub 2020 Jan 15. PubMed PMID: 31937234; PubMed Central PMCID: PMC7014796.
- Dixit HG, Starr R, Dundon ML, Pairs PI, Yang X, Zhang Y, Nampe D, Ballas CB, Tsutsui H, Forman SJ, Brown CE, Rao MP. Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery. Nano Lett. 2020 Feb 12;20(2):860-867. DOI: 10.1021/acs.nanolett.9b03175. Epub 2019 Oct 28. PubMed PMID: 31647675. Weist MR, Starr R,
- Aguilar B, Shea J, Miles J, Poku E, Gerdts E, Yang X, Pricman S, Forman SJ, Colcher D, Brown CE, Shively J. (2018) Positron emission tomography of adoptively transferred chimeric antigen receptor T cells with Zirconium-89 oxine. J Nucl Med. 59(10): 1531-1537.
- Brown CE, Aguilar B, Starr R, Yang X, Chang WC, Weng L, Chang B, Sarkissian A, Brito A, Sanchez JF, Ostberg JR, D'Apuzzo M, Badie B, Barish ME, Forman SJ. Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma. Mol Ther. 2018 Jan 3;26(1):31-44. DOI: 10.1016/j.ymthe.2017.10.002. Epub 2017 Oct 5. PubMed PMID: 29103912; PubMed Central PMCID: PMC5763077.
- Priceman SJ, Gerdts EA, Tilakawardane D, Kennewick KT, Murad JP, Park AK, Jeang B, Yamaguchi Y, Yang X, Urak R, Weng L, Chang WC, Wright S, Pal S, Reiter RE, Wu AM, Brown CE, Forman SJ. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer. Oncoimmunology. 2018;7(2):e1380764. DOI: 10.1080/2162402X.2017.1380764. eCollection 2018. PubMed PMID: 29308300; PubMed Central PMCID: PMC5749625.
- Keu KV, Witney TH, Yaghoubi S, Rosenberg J, Kurien A, Magnusson R, Williams J, Habte F, Wagner JR, Forman S, Brown C, Allen-Auerbach M, Czernin J, Tang W, Jensen MC, Badie B, Gambhir SS. Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma. Sci Transl Med. 2017 Jan 18;9(373). DOI: 10.1126/scitranslmed.aag2196. PubMed PMID: 28100832; PubMed Central PMCID: PMC5260938.
- Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, Norris AP, Wong CW, Urak RZ, Chang WC, Khaled SK, Siddiqi T, Budde LE, Xu J, Chang B, Gidwaney N, Thomas SH, Cooper LJ, Riddell SR, Brown CE, Jensen MC, Forman SJ. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980-90. DOI: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26. PubMed PMID: 27118452; PubMed Central PMCID: PMC4911862.
- Brown CE, Badie B, Barish ME, Weng L, Ostberg JR, Chang WC, Naranjo A, Starr R, Wagner J, Wright C, Zhai Y, Bading JR, Ressler JA, Portnow J, D'Apuzzo M, Forman SJ, Jensen MC. Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clin Cancer Res. 2015 Sep 15;21(18):4062-72. DOI: 10.1158/1078-0432.CCR-15-0428. Epub 2015 Jun 9. PubMed PMID: 26059190; PubMed Central PMCID: PMC4632968.
Lab Field Reviews
- Brown CE, Mackall CL. CAR T cell therapy: inroads to response and resistance. Nat Rev Immunol. 2019 Feb;19(2):73-74. DOI: 10.1038/s41577-018-0119-y. Review. PubMed PMID: 30631206.
- Akhavan D, Alizadeh D, Wang D, Weist MR, Shepphird JK, Brown CE. CAR T cells for brain tumors: Lessons learned and road ahead. Immunol Rev. 2019 Jul;290(1):60-84. DOI: 10.1111/imr.12773. Review. PubMed PMID: 31355493; PubMed Central PMCID: PMC6771592.
To view more of Christine Brown's publications, please visit Christine Brown's full bibliography