My role as a lead investigator on the “Pediatric Leukemia Adoptive Therapy (PLAT)-01” Phase I clinical study will be to facilitate the clinical translation of advances in T cell genetic engineering to improve the prognosis of children with relapsed acute lymphoblastic leukemia. Building on my laboratory’s preclinical modeling, cGMP process development, and clinical experience in early phase IND supported T cell adoptive therapy trials, I will support the translational and clinical activities proposed in this study. My clinical training in pediatric hematology-oncology and hematopoietic cell transplantation in Seattle and laboratory research training under the mentorship of Dr. Philip D Greenberg at the FHCRC and extensive collaborative work with Dr. Stan Riddell have provided me the research and clinical skill set to be an effective investigator on this clinical study. I am currently Director of the Ben Towne Center for Childhood Cancer at Seattle Children’s Research Institute. In addition, I hold an appointment at the University of Washington School of Medicine as Professor of Pediatrics in the Division of Pediatric Hematology-Oncology, with a Joint Membership to the Fred Hutchinson Cancer Research Center Program in Immunology. Since establishing an independent research program 13 years ago at City of Hope, I have lead five FDA-authorized investigator-initiated IND supported human clinical trials employing genetically modified T-cell adoptive immunotherapy, one of which was a pilot first-in-human trial using CD19-specific CTL adoptive transfer for follicular lymphoma.
Positions and Honors.
Positions and Employment
1993-1997 Fellow, Pediatric Hematology/Oncology, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA (Three year research component- Program in Immunology, FHCRC/Mentor- Dr. Philip D. Greenberg)
1997-2004 Assistant Professor, Pediatrics, COHNMC, Duarte, CA
2002-2010 Program Leader, Cancer Immunotherapeutics Program, City of Hope NCI-designated Comprehensive Cancer Center
2009-Present External Advisory Board, European Union Framework Programme Six Integrated Project
2009-Present Scientific Advisory Board, Forbeck Foundation
2010-Present Member, American Pediatric Society
ASBMT Ernest McCullock and James Till Award
Society for Pediatric Research Young Investigator Award
STOP CANCER Foundation Career Advancement Award
Selected peer-reviewed publications(selected from 54 peer reviewed publications)
Most relevant to the current application Cooper, L.N., Topp, M.S., Serrano, L.M., Gonzalez, S., Chang, W.C., Naranjo, A., Wright, C., Popplewell, L., Raubitschek, A., Forman, S.J., Jensen, M.C.: T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood 2003;101(4):1637-44.
Chen, Y.C., Jensen, M.C.†, Smolke, C.D.†: Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Proc Natl Acad Sci USA 2010;107(19):8531-8536. PMCID: PMC2889348 (†M.C.J. and C.D.S. designated equal contributors to work as senior authors).
Wang, X., Berger, C., Wong, C.W., Forman, S.J., Riddell, S.R., Jensen, M.C.: Engraftment of human central memory-derived effector CD8+ T cells in immunodeficient mice. Blood 2011;117(6):1888-98. PMCID: PMC3056638
Wang, X., Chang, C.W., Colcher, D., Sherman, M, Ostberg, J.R., Riddell, S.R., Jensen, M.C.: A transgene encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 2011; 118(5):1255-63. PMCID: PMC3152493
Terakura, S., Yamamoto, T.N., Gardner, R.A., Turtle, C.J., Jensen, M.C., Riddell, S.R.: Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory cells. Blood 2011;119(1):72-82. PMCID: PMC3251238
Additional recent publications of importance to the field (in chronological order) Jensen, M., Tan, G., Forman, S., Wu, A.M., and Raubitschek, A.: CD20 is a molecular target for scFvFc:z receptor re-directed T cells: implications for cellular immunotherapy of CD20+ malignancy. Biology of Blood and Marrow Transplantation, 4:75-83, 1998.
Jensen, M. C., Clarke, P., Tan, G., Wright, C., Chung-Chang, W., Clark, T.N. , Zhang, F., Slovak, M.L., Wu, A.M., Forman, S.J., and Raubitschek, A.: Human T Lymphocyte genetic modification with naked DNA. Mol Therapy, 1(1):49-55, 2000.
Jensen, M.C., Cooper, L.J.N., Wu, A.M., Forman, S.J., and Raubitschek, A.: Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-Cell malignancy. Cytotherapy, 5(2):131-138, 2003.
Wang, J., Press, O.W., Lindgren, C.G., Greenberg, P., Riddell, S., Qian, X., Laugen, C., Raubitschek, A., Forman, S.J., and Jensen, M.C.: Cellular immunotherapy for follicular lymphoma using genetically modified CD20-specific CD8+ cytotoxic T lymphocytes. Molecular Therapy, 9(4) 577-86, 2004.
Cooper, L.J., Al-Kadhimi, Z., DiGiusto, D., Kalos, M., Colcher, D., Raubitschek, A., Forman, S.J., and Jensen,M.C.: Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. Blood Cells, Molecules, & Diseases. 33(1):83-89, 2004.
Cooper, L.J.N., Topp, M.S., Pinzon, C, Jensen,M.C., Riddell, S.R., and Greenberg P.D.: Enhanced transgene expression in quiescent and activated human CD8+ T cells. Human Gene Therapy. 15(7):648-58, 2004.
Cooper, L.J.N., Al-Kadhimi, Z., Serrano, L.M., Pfeiffer, T., Olivares, S., Castro, A., Chang, W.-C., Gonzalez, S., Smith, D., Forman, S.J., and Jensen, M.C.: Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTL's by co-transfer of T cells modified to present influenza MP1. Blood, 105(4):1622-31, 2005.
Serrano, L.M., Pfeiffer, T., Olivares, S. Numbenjapon, T., Bennitt, J., Kim, D., Smith, D., McNamara, G., Al-Kadhimi, Z., Rosenthal, J., Forman, S.J. Jensen, M.C. and Cooper, L.J.: Differentiation of naïve cord blood T cells into CD19-specific cytolytic effectors for post-transplant adoptive immunotherapy. Blood; 107(7):2643-52, 2006. PMCID: PMC1895371
Kowolik, C.M., Topp, M.S., Gonzalez, S., Pfeiffer, T., Olivares, S., Gonzalez, N., Smith, D.D., Forman, S., Jensen, M.C., and Cooper, L.J.: CD28 constimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Research, 66(22):10995-1004, 2006.
Park, J.R., DiGiusto, D.L., Slovak, M., Wright, C., Naranjo, A., Wagner, J., Meechoovet, H.B., Bautista, C., Chang, W.C., Ostberg, J.R., and Jensen, M.C.: Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Molecular Ther, 15(4):825-33, 2007.
Wang, J., Jensen, M., Lin, Y., Sui, X., Chen, E., Lindgren, C.G., Till, B., Raubitschek, A., Forman, S.J., Qian, X., James, S., Greenberg, P., Riddell, S., Press, O.W.: Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains. Hu Gene Ther. 18(8):712-25, 2007.
Chang, L., Chang, W.C., McNamara, G., Aguilar, B., Ostberg, J.R., and Jensen, M.C.: Transgene Enforced Costimulation of CD4+ T cells leads to Enhanced and Sustained Anti-Tumor Effector Functioning. Cytother., 2007;9:771-84.
Berger, C., Jensen, M.C., Lansdorp, P.M., Gough, M., Elliott, C., Riddell, S.R.: Adoptive transfer of effector CD8 T cells derived from central memory cells establishes persistent T cell memory in primates. J. Clin. Investigation, 2008;118(1):294-305. PMCID: PMC2104476
Jensen, M.C., Popplewell, L., Cooper, L.J., DiGiusto, D., Kalos, M., Ostberg, J.R., Forman, S.J.: Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol. Of Blood & Marrow Transplantation, 2010:16(9):1245-56. PMCID: in progress.
Till, B.G., Jensen, M.C., Wang J., Qian, X., Gopal, A.K., Maloney, D.G., Lindgren C.G., Lin, Y., Pagel, J.M., Budde, L.E., Raubitschek, A., Forman, S.J., Greenberg, P.D., Riddell, S.R., Press, O.W.; CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood, 2012: in press.
Targeted therapy of ALL with gene-modified central memory T Cells
Specific Aim 1, to determine the safety and anti-tumor activity of adoptive therapy with donor Tcm-derived bio-specific (CMVpp65xCD19) Te clones for patients with CD19+ ALL following HLA matched allogeneic HCT. Specific Aim 2, to determine the safety and anti-tumor activity of adoptive therapy with autologous Tcm-derived bi-specific (CMVpp65xCD19) polyclonal Te cells for patients with CD19+ ALL following autologous HCT.
Role: Co-PI with Dr. Stanley Riddell, FHCRC
P50 CA107399-05 Forman (PI)
City of Hope Lymphoma SPORE
This is a Specialized Program of Research Excellence for the development of translation projects. Project 2 focuses on the development of lymphoma targeting adoptive therapy using genetically modified CD19-specific T-cells that express second-generation antigen receptor chimeras having both activation and co-stimulatory modules.