Journal of Experimental Hematology % - 40%

Size: px

Start display at page:

Download "Journal of Experimental Hematology % - 40%"

Meredith Osborne
7 years ago
Views:

1 Journal of Experimental Hematology Article ID T CAR - T B / * B / B / CD20 B / 20% - 40% 5 B CD19 T CAR-T CD19 CAR-T B CAR-T B / CD19 CAR-T B / B T R R A doi /j. issn Clinical Translational Re se arch of Chime ric Antige n Re ce ptor-t CAR-T Cells for the Treatment of Relapsed and Refractory B-ce ll Lymphoma / Le uke mia Review YUAN Shun-Zong SU Hang * Department of Lymphoma Head and Neck Cancer Affiliated Hospital of Academy of Military Medical Sciences Beijing China * Corresponding Author SU Hang Senior Physician Associate Professor. suhang307@ 126. com Abstract B-cell lymphoma and leukemia are the most common subtypes of malignant lymphomas. Relapse and refractory to multiple therapy are the main reasons of treatment failure. As the classical anti-tumor methods surgery radiation chemotherapy and palliative therapy have cured lots of cancer patients. However each year many patients still died of different kinds of hard-to-treat cancers. Although the ratio of complete remission of B-cell lymphoma / leukemia patients particularly with CD20 positive mature B cell malignancies has been largely increased after the application of Rituximab in clinic nearly 20% - 40% patients still died due to relapse and refractory to the treatment. During last five years the development of chimeric antigen receptor-t CAR-T cells especially CD19 CAR-T cells which can recognize CD19 specifically expressed on B cells and have been demonstrated to be significantly effective to relapsed and refractory B cell lymphoma /leukemia in clinical trials has gradually attracted extensively concerning from researchers and clinicians. Many medical institutions all over the world besides in China have registered the clinical trials for B- cell lymphoma /leukemia patients by use of CAR-T cells. In this review we summarize the developmental history the main ongoing clinical trials and proved potential adverse affects of CD19 CAR-T cells for the treatment of patients with B-cell lymphoma / leukemia. Key words B-cell lymphoma leukemia chimeric antigen receptor-t cell J Exp Hematol B T NK 85% 1 WHO 90% B / *. suhang307@ 126. com

2 1138 Journal of Experimental Hematology CD20 B CAR CD3ζ / / B FcγRIIIAγ CAR-T 5 / Hwu 6-7 Stancovski 7 TNP scfv MOv18 Her2 scfv 76% 1-2 B / CAR-T MOv18 Her2 20% - 30% Zelig Eshhar CAR-T 1-2 B / 1998 Jensen 8 CD20 scfv CAR-T CD Cooper 9 CD19 scfv CD8 + CAR-T B B-ALL I 2006 Kowolik CD19 CAR-T CD28 scfv CD3ζ T 2 CAR-T Carpenito 11 CAR CD137 CAR-T 2011 Carl June T CAR-T Zhong 12 2 B 2 CAR-T B CAR-T 13 Kochenderfer / CAR-T 14 2 CAR-T IL-2 IFN-γ 3 CAR-T CAR-T 300 Carl June Michel Sadelain Steven A. Rosenberg Cooper B / CAR-T CAR-T B CAR-T B CAR-T CAR-T 1989 Gross 4 TNP 2008 Till 15 1 CD20 scfv 1 CAR-T T TCR α β CAR-T T T B 5 TNP B CD20 CAR-T 1993 TNP 2012 Till 16 scfv CD3ζ /FcγRIIIAγ 3 3 CD20 CAR-T T CTL TNP CAR-T TNP B

3 T CAR-T B / 1139 CD19 CD19 CAR-T B B-ALL / 2010 Kochenderfer CD anti-cd19 CAR-T CD19 CAR-T 32 CD Kalos 18 Porter 19 Carl June 3 CD19 CAR-T 3 B B CAR-T B-CLL Brentjens 20 Michel Sadelain B CAR-T 2 CD19 CAR-T 8 B- CLL 1 B B-ALL CAR-T 1 6 Savoldo 21 Gianpietro Dotti 2 CD19 CAR-T 5 B B CD19 CD19 CAR-T B CAR-T 2 / Brentjens h 2012 Kochenderfer 22 2 CD19 CAR-T 8 / 1 44 h 7 1 Kochenderfer B-CLL 18 d Brentjens 2 Michel Brentjens 2 Sadelain 5 B-ALL 2 CD19 CAR-T Grupp 23 Carl June 28 3 CD19 CAR-T 2 B-ALL 1 23 Davila 25 Michel Sadelain Kochenderfer 24 Steven A. Rosenberg 2 CD19 CAR- C - B T 10 B / B-CLL CAR-T Davila 25 Michel Sadelain 16 / B ALL 2 CD19 CAR-T 15 CD19 CAR-T 88% CD19 CAR-T CD19 CAR-T B / CAR-T CAR-T anti-cd19 CAR-T B CAR-T B-ALL T

4 1140 Journal of Experimental Hematology T Brentjens RJ Davila ML Riviere I et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-re- Sci Transl Med mrna fractory acute lymphoblastic leukemia Rosenberg ra138. T visited. Nat Rev Drug Discov FDA T CAR-T CAR-T 33 Med receptors. J Immunol Maxcyte CAR-T mrna % 50 ml mrna cells. Cancer Res B CAR-T eradication. Mol Ther cancer therapy. Nat Rev Cancer B Immunother CAR-T 15 Till BG Jensen MC Wang J 1 Cheson BD Leonard JP. Monoclonal antibody therapy for B-cell non-hodgkin's lymphoma. N Engl J Med Lesterhuis WJ Haanen JB Punt CJ. Cancer immunotherapy re- 4 Gross G Waks T Eshhar Z. Expression of immunoglobulin-t-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA Eshhar Z Waks T Gross G et al. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA Hwu P Shafer GE Treisman J et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. J Exp 7 Stancovski I Schindler DG Waks T et al. Targeting of T lymphocytes to Neu / HER2-expressing cells using chimeric single chain Fv 8 Jensen M Tan G Forman S et al. CD20 is a molecular target for scfvfc zeta receptor redirected T cells implications for cellular immunotherapy of CD20 + malignancy. Biol Blood Marrow Transplant 9 Cooper LJ Topp MS Serrano LM et al. T-cell clones can be rendered specific for CD19 toward the selective augmentation of the graft-versus-b-lineage leukemia effect. Blood Kowolik CM Topp MS Gonzalez S et al. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T 11 Carpenito C Milone MC Hassan R et al. Control of large established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci USA Zhong XS Matsushita M Plotkin J et al. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase / AKT / Bcl-XL activation and CD8 + T cell-mediated tumor 13 Kershaw MH Westwood JA Darcy PK. Gene-engineered T cells for 14 Kochenderfer JN Feldman SA Zhao Y et al. Construction and preclinical evaluation of an anti-cd19 chimeric antigen receptor. J et al. Adoptive immunotherapy for indolent non-hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood Till BG Jensen MC Wang J et al. CD20-specific adoptive immu-

5 T CAR-T B / 1141 notherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains pilot clinical trial results Blood 17 Kochenderfer JN Wilson WH Janik JE et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood Kalos M Levine BL Porter DL et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med ra Porter DL Levine BL Kalos M et al. Chimeric antigen receptormodified T cells in chronic lymphoid leukemia. N Engl J Med Brentjens RJ Riviere I Park JH et al. Safety and persistence of a- doptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood Savoldo B Ramos CA Liu E et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest Kochenderfer JN Dudley ME Feldman SA et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-cd19 chimeric-antigen-receptor-transduced T cells. Blood Grupp SA Kalos M Barrett D et al. Chimeric antigen receptormodified T cells for acute lymphoid leukemia. N Engl J Med Kochenderfer JN Dudley ME Carpenter RO et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood Davila ML Riviere I Wang X et al. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med ra Le Viseur C Hotfilder M Bomken S et al. In childhood acute lymphoblastic leukemia blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell Brentjens R Yeh R Bernal Y et al. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells case report of an unforeseen adverse event in a phase I clinical trial. Mol T- her Barrett DM Singh N Porter DL et al. Chimeric antigen receptor therapy for cancer. Annu Rev Med Budde LE Berger C Lin Y et al. Combining a CD20 Chimeric Antigen Receptor and an Inducible Caspase 9 Suicide Switch to Improve the Efficacy and Safety of T Cell Adoptive Immunotherapy for Lymphoma. PLoS One e Hoyos V Savoldo B Quintarelli C et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma /leukemia effects and safety. Leukemia Rosenberg SA Aebersold P Cornetta K et al. Gene transfer into humans immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med Hoyos V Savoldo B Dotti G. Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. Haematologica Singh H Figliola MJ Dawson MJ et al. Manufacture of clinicalgrade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells. PLoS One e Li LH Shivakumar R Feller S et al. Highly efficient large volume flow electroporation. Technol Cancer Res Treat Li L Liu LN Feller S et al. Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method. Cancer Gene Ther

Chimeric Antigen Receptor T Cell Therapy

Chimeric Antigen Receptor T Cell Therapy Yi Lin, MD, PhD Mayo Clinic, Rochester, MN Alliance Spring Group Meeting - May 13, 2016 Presentation Objectives l Scientific overview of chimeric antigen receptor