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Circumventing CD19 antigen loss

Chimeric antigen receptor (CAR) T cell treatment for B cell malignancies was pioneered with CD19-targeted CAR T cells. Despite robust clinical responses, relapse due to CD19 antigen loss is common. Qin et al. examined B cell activating factor receptor (BAFF-R) as an alternate CAR T cell target. BAFF-R–targeted CAR T cells could kill multiple human lymphoma and leukemia cell lines, either in vitro or in mice, as well as patient-derived samples. The BAFF-R-CAR T cells could also eradicate tumors lacking CD19. Their compelling preclinical results support the clinical development of BAFF-R–targeted CAR T cells for combating B cell malignancies.

Abstract

CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy. We developed humanized, second-generation CAR T cells against another B cell–specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia (ALL) lines. Adoptively transferred BAFF-R-CAR T cells eradicated 10-day preestablished tumor xenografts after a single treatment and retained efficacy against xenografts deficient in CD19 expression, including CD19-negative variants within a background of CD19-positive lymphoma cells. Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells. BAFF-R-CAR, but not CD19-CAR, T cells also demonstrated antitumor effects against an additional CD19 antigen loss primary patient–derived xenograft (PDX) in vivo. BAFF-R is amenable to CAR T cell therapy, and its targeting may prevent emergence of CD19 antigen loss variants.
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Supplementary Material

Summary

Fig. S1. Cytokine release assay.
Fig. S2. BAFF-R-CAR T cell in vitro cytotoxic T lymphocyte assay.
Fig. S3. Preliminary BAFF-R-CAR T cell assessment in vivo.
Fig. S4. CAR T cells validated for CAR expression and cytotoxic T lymphocyte activity.
Fig. S5. CD19-KO clone selection.
Data file S1. Primary data.

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References and Notes

1
J. N. Brudno, J. N. Kochenderfer, Chimeric antigen receptor T-cell therapies for lymphoma. Nat. Rev. Clin. Oncol. 15, 31–46 (2018).
2
D. Sommermeyer, T. Hill, S. M. Shamah, A. I. Salter, Y. Chen, K. M. Mohler, S. R. Riddell, Fully human CD19-specific chimeric antigen receptors for T-cell therapy. Leukemia 31, 2191–2199 (2017).
3
J. H. Park, I. Rivière, M. Gonen, X. Wang, B. Sénéchal, K. J. Curran, C. Sauter, Y. Wang, B. Santomasso, E. Mead, M. Roshal, P. Maslak, M. Davila, R. J. Brentjens, M. Sadelain, Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl. J. Med. 378, 449–459 (2018).
4
S. L. Maude, N. Frey, P. A. Shaw, R. Aplenc, D. M. Barrett, N. J. Bunin, A. Chew, V. E. Gonzalez, Z. Zheng, S. F. Lacey, Y. D. Mahnke, J. J. Melenhorst, S. R. Rheingold, A. Shen, D. T. Teachey, B. L. Levine, C. H. June, D. L. Porter, S. A. Grupp, Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507–1517 (2014).
5
X. Wang, L. L. Popplewell, J. R. Wagner, A. Naranjo, M. S. Blanchard, M. R. Mott, A. P. Norris, C. W. Wong, R. Z. Urak, W.-C. Chang, S. K. Khaled, T. Siddiqi, L. E. Budde, J. Xu, B. Chang, N. Gidwaney, S. H. Thomas, L. J. Cooper, S. R. Riddell, C. E. Brown, M. C. Jensen, S. J. Forman, Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood 127, 2980–2990 (2016).
6
M. Ruella, D. M. Barrett, S. S. Kenderian, O. Shestova, T. J. Hofmann, J. Perazzelli, M. Klichinsky, V. Aikawa, F. Nazimuddin, M. Kozlowski, J. Scholler, S. F. Lacey, J. J. Melenhorst, J. J. D. Morrissette, D. A. Christian, C. A. Hunter, M. Kalos, D. L. Porter, C. H. June, S. A. Grupp, S. Gill, Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J. Clin. Invest. 126, 3814–3826 (2016).
7
E. Sotillo, D. M. Barrett, K. L. Black, A. Bagashev, D. Oldridge, G. Wu, R. Sussman, C. Lanauze, M. Ruella, M. R. Gazzara, N. M. Martinez, C. T. Harrington, E. Y. Chung, J. Perazzelli, T. J. Hofmann, S. L. Maude, P. Raman, A. Barrera, S. Gill, S. F. Lacey, J. J. Melenhorst, D. Allman, E. Jacoby, T. Fry, C. Mackall, Y. Barash, K. W. Lynch, J. M. Maris, S. A. Grupp, A. Thomas-Tikhonenko, Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 5, 1282–1295 (2015).
8
J. M. Hildebrand, Z. Luo, M. K. Manske, T. Price-Troska, S. C. Ziesmer, W. Lin, B. S. Hostager, S. L. Slager, T. E. Witzig, S. M. Ansell, J. R. Cerhan, G. A. Bishop, A. J. Novak, A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. J. Exp. Med. 207, 2569–2579 (2010).
9
J. S. Thompson, S. A. Bixler, F. Qian, K. Vora, M. L. Scott, T. G. Cachero, C. Hession, P. Schneider, I. D. Sizing, C. Mullen, K. Strauch, M. Zafari, C. D. Benjamin, J. Tschopp, J. L. Browning, C. Ambrose, BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 293, 2108–2111 (2001).
10
A. J. Novak, D. M. Grote, M. Stenson, S. C. Ziesmer, T. E. Witzig, T. M. Habermann, B. Harder, K. M. Ristow, R. J. Bram, D. F. Jelinek, J. A. Gross, S. M. Ansell, Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: Correlation with disease activity and patient outcome. Blood 104, 2247–2253 (2004).
11
C. V. Lee, S. G. Hymowitz, H. J. Wallweber, N. C. Gordon, K. L. Billeci, S.-P. Tsai, D. M. Compaan, J. Yin, Q. Gong, R. F. Kelley, L. E. DeForge, F. Martin, M. A. Starovasnik, G. Fuh, Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells. Blood 108, 3103–3111 (2006).
12
R. Parameswaran, M. Lim, F. Fei, H. Abdel-Azim, A. Arutyunyan, I. Schiffer, M. E. McLaughlin, H. Gram, H. Huet, J. Groffen, N. Heisterkamp, Effector-mediated eradication of precursor B acute lymphoblastic leukemia with a novel fc-engineered monoclonal antibody targeting the BAFF-R. Mol. Cancer Ther. 13, 1567–1577 (2014).
13
H. Qin, G. Wei, I. Sakamaki, Z. Dong, W. A. Cheng, D. L. Smith, F. Wen, H. Sun, K. Kim, S. Cha, L. Bover, S. S. Neelapu, L. W. Kwak, Novel BAFF-receptor antibody to natively folded recombinant protein eliminates drug-resistant human B-cell malignancies in vivo. Clin. Can Res. 24, 1114–1123 (2018).
14
X. Wang, A. Naranjo, C. E. Brown, C. Bautista, C. W. Wong, W. C. Chang, B. Aguilar, J. R. Ostberg, S. R. Riddell, S. J. Forman, M. C. Jensen, Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale. J. Immunother. 35, 689–701 (2012).
15
X. Wang, C. Berger, C. W. Wong, S. J. Forman, S. R. Riddell, M. C. Jensen, Engraftment of human central memory-derived effector CD8+ T cells in immunodeficient mice. Blood 117, 1888–1898 (2011).
16
M. Sabatino, J. Hu, M. Sommariva, S. Gautam, V. Fellowes, J. D. Hocker, S. Dougherty, H. Qin, C. A. Klebanoff, T. J. Fry, R. E. Gress, J. N. Kochenderfer, D. F. Stroncek, Y. Ji, L. Gattinoni, Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood 128, 519–528 (2016).
17
C. S. Hinrichs, Z. A. Borman, L. Gattinoni, Z. Yu, W. R. Burns, J. Huang, C. A. Klebanoff, L. A. Johnson, S. P. Kerkar, S. Yang, P. Muranski, D. C. Palmer, C. D. Scott, R. A. Morgan, P. F. Robbins, S. A. Rosenberg, N. P. Restifo, Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood 117, 808–814 (2011).
18
M. Schmueck-Henneresse, B. Omer, T. Shum, H. Tashiro, M. Mamonkin, N. Lapteva, S. Sharma, L. Rollins, G. Dotti, P. Reinke, H. D. Volk, C. M. Rooney, Comprehensive approach for identifying the T cell subset origin of CD3 and CD28 antibody-activated chimeric antigen receptor-modified T cells. J. Immunol. 199, 348–362 (2017).
19
L. Gattinoni, E. Lugli, Y. Ji, Z. Pos, C. M. Paulos, M. F. Quigley, J. R. Almeida, E. Gostick, Z. Yu, C. Carpenito, E. Wang, D. C. Douek, D. A. Price, C. H. June, F. M. Marincola, M. Roederer, N. P. Restifo, A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290–1297 (2011).
20
S. J. Schuster, J. Svoboda, E. A. Chong, S. D. Nasta, A. R. Mato, O. Anak, J. L. Brogdon, I. Pruteanu-Malinici, V. Bhoj, D. Landsburg, M. Wasik, B. L. Levine, S. F. Lacey, J. J. Melenhorst, D. L. Porter, C. H. June, Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 377, 2545–2554 (2017).
21
S. Shojaee, R. Caeser, M. Buchner, E. Park, S. Swaminathan, C. Hurtz, H. Geng, L. N. Chan, L. Klemm, W.-K. Hofmann, Y. H. Qiu, N. Zhang, K. R. Coombes, E. Paietta, J. Molkentin, H. P. Koeffler, C. L. Willman, S. P. Hunger, A. Melnick, S. M. Kornblau, M. Müschen, Erk negative feedback control enables pre-B cell transformation and represents a therapeutic target in acute lymphoblastic leukemia. Cancer Cell 28, 114–128 (2015).
22
S. Xie, J. Duan, B. Li, P. Zhou, G. C. Hon, Multiplexed engineering and analysis of combinatorial enhancer activity in single cells. Mol. Cell 66, 285–299.e5 (2017).
23
M. A. Horlbeck, L. A. Gilbert, J. E. Villalta, B. Adamson, R. A. Pak, Y. Chen, A. P. Fields, C. Y. Park, J. E. Corn, M. Kampmann, J. S. Weissman, Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. Elife 5, e19760 (2016).
24
H. Kantarjian, A. Stein, N. Gökbuget, A. K. Fielding, A. C. Schuh, J.-M. Ribera, A. Wei, H. Dombret, R. Foà, R. Bassan, Ö. Arslan, M. A. Sanz, J. Bergeron, F. Demirkan, E. Lech-Maranda, A. Rambaldi, X. Thomas, H.-A. Horst, M. Brüggemann, W. Klapper, B. L. Wood, A. Fleishman, D. Nagorsen, C. Holland, Z. Zimmerman, M. S. Topp, Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376, 836–847 (2017).
25
L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. T. Tamayo, L. C. Yoshimura, R. J. Ford, BAFF-R promotes cell proliferation and survival through interaction with IKKβ and NF-κB/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells. Blood 113, 4627–4636 (2009).
26
L. V. Pham, L. Fu, A. T. Tamayo, C. Bueso-Ramos, E. Drakos, F. Vega, L. J. Medeiros, R. J. Ford, Constitutive BR3 receptor signaling in diffuse, large B-cell lymphomas stabilizes nuclear factor-κB-inducing kinase while activating both canonical and alternative nuclear factor-κB pathways. Blood 117, 200–210 (2011).
27
Y.-J. Li, W.-Q. Jiang, H.-L. Rao, J.-J. Huang, Y. Xia, H.-Q. Huang, T.-Y. Lin, Z.-J. Xia, S. Li, Z.-M. Li, Expression of BAFF and BAFF-R in follicular lymphoma: Correlation with clinicopathologic characteristics and survival outcomes. PloS one 7, e50936 (2012).
28
X. Shen, M. Wang, Y. Guo, S. Ju, The correlation between non-Hodgkin lymphoma and expression levels of B-cell activating factor and its receptors. Adv. Clin. Exp. Med. 25, 837–844 (2016).
29
R. Parameswaran, M. Müschen, Y.-m. Kim, J. Groffen, N. Heisterkamp, A functional receptor for B-cell–activating factor is expressed on human acute lymphoblastic leukemias. Cancer Res. 70, 4346–4356 (2010).
30
D. J. Miller, C. E. Hayes, Phenotypic and genetic characterization of a unique B lymphocyte deficiency in strain a/WySnJ mice. Eur. J. Immunol. 21, 1123–1130 (1991).
31
Y. Sasaki, S. Casola, J. L. Kutok, K. Rajewsky, M. Schmidt-Supprian, TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology. J. Immunol. 173, 2245–2252 (2004).
32
S. J. Rodig, A. Shahsafaei, B. Li, C. R. Mackay, D. M. Dorfman, BAFF-R, the major B cell–activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. Hum. Pathol. 36, 1113–1119 (2005).
33
N. Nakamura, H. Hase, D. Sakurai, S. Yoshida, M. Abe, N. Tsukada, J. Takizawa, S. Aoki, M. Kojima, S. Nakamura, T. Kobata, Expression of BAFF-R (BR 3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody. Virchows Arch. 447, 53–60 (2005).
34
J. C. Paterson, S. Tedoldi, A. Craxton, M. Jones, M. L. Hansmann, G. Collins, H. Roberton, Y. Natkunam, S. Pileri, E. Campo, E. A. Clark, D. Y. Mason, T. Marafioti, The differential expression of LCK and BAFF-receptor and their role in apoptosis in human lymphomas. Haematologica 91, 772–780 (2006).
35
A. Davidson, Targeting BAFF in autoimmunity. Curr. Opin. Immunol. 22, 732–739 (2010).
36
R. Furie, M. Petri, O. Zamani, R. Cervera, D. J. Wallace, D. Tegzova, J. Sanchez-Guerrero, A. Schwarting, J. T. Merrill, W. W. Chatham, W. Stohl, E. M. Ginzler, D. R. Hough, Z. J. Zhong, W. Freimuth, R. F. van Vollenhoven; B.-S. Group, A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 63, 3918–3930 (2011).
37
G. Fazio, N. Turazzi, V. Cazzaniga, M. Kreuzaler, O. Maglia, C. F. Magnani, E. Biagi, A. Rolink, A. Biondi, G. Cazzaniga, TNFRSF13C (BAFFR) positive blasts persist after early treatment and at relapse in childhood B-cell precursor acute lymphoblastic leukaemia. Br. J. Haematol. 182, 434–436 (2018).
38
E. M. McWilliams, C. R. Lucas, T. Chen, B. K. Harrington, R. Wasmuth, A. Campbell, K. A. Rogers, C. M. Cheney, X. Mo, L. A. Andritsos, F. T. Awan, J. Woyach, W. E. Carson III, J. Butchar, S. Tridandapani, E. Hertlein, C. E. Castro, N. Muthusamy, J. C. Byrd, Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib. Blood Adv. 3, 447–460 (2019).
39
N. Turazzi, G. Fazio, V. Rossi, A. Rolink, G. Cazzaniga, A. Biondi, C. F. Magnani, E. Biagi, Engineered T cells towards TNFRSF13C (BAFFR): A novel strategy to efficiently target B-cell acute lymphoblastic leukaemia. Br. J. Haematol. 182, 939–943 (2018).
40
M. Ruella, M. V. Maus, Catch me if you can: Leukemia escape after CD19-directed T cell immunotherapies. Comput. Struct. Biotechnol. J. 14, 357–362 (2016).
41
T. J. Fry, N. N. Shah, R. J. Orentas, M. Stetler-Stevenson, C. M. Yuan, S. Ramakrishna, P. Wolters, S. Martin, C. Delbrook, B. Yates, H. Shalabi, T. J. Fountaine, J. F. Shern, R. G. Majzner, D. F. Stroncek, M. Sabatino, Y. Feng, D. S. Dimitrov, L. Zhang, S. Nguyen, H. Qin, B. Dropulic, D. W. Lee, C. L. Mackall, CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 24, 20–28 (2018).
42
N. N. Shah, M. S. Stevenson, C. M. Yuan, K. Richards, C. Delbrook, R. J. Kreitman, I. Pastan, A. S. Wayne, Characterization of CD22 expression in acute lymphoblastic leukemia. Pediatr. Blood Cancer 62, 964–969 (2015).
43
J. Rosenthal, A. S. Naqvi, G. Wertheim, M. Paessler, S. R. Rheingold, A. Thomas-Tikhonenko, V. Pillai, Semi–quantitative analysis of CD19 and CD22 expression in B–lymphoblastic leukemia and implications for Targeted immunotherapy. Blood 130, 1331–1331 (2017).

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Science Translational Medicine
Volume 11 | Issue 511
September 2019

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Received: 7 February 2019
Accepted: 31 July 2019

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Acknowledgments

Research reported in this publication included work performed in the Analytical Cytometry Core, Hematopoietic Tissue Biorepository Core, Integrative Genomics Core, and Small Animal Imaging Core supported by the National Cancer Institute of the NIH under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank the Sandra and Edward Meyer Cancer Center PDTX Shared Resource for their support. Funding: We are grateful for the support from the Toni Stephenson Lymphoma Center at Beckman Research Institute of City of Hope. The study was also supported by the Leukemia and Lymphoma Society (LLS): Translational Research Program (TRP 6540-18; PI: L.W.K.), Mantle Cell Lymphoma Research Initiative (MCL 7000-18; PI: L.W.K.), and SCOR grants (SCOR 7011-16 and 7012-16; PI: G.G.I.); the NIH/NCI (SPORE 2P50CA107399; PIs: S.J.F. and L.W.K.; 1R21CA223141; PI: H.Q.); the Department of Defense (CA170783; PI: L.W.K.); and the Hope Portfolio Fund at City of Hope (PI: H.Q.). Research in the Müschen laboratory is funded by the NIH/NCI through the Outstanding Investigator Award R35CA197628 (to M.M.), U10CA180827 (to M.M.), R01CA137060, R01CA157644, R01CA172558, and R01CA213138 (to M.M.); the Howard Hughes Medical Institute HHMI-55108547 (to M.M.); and the Falk Trust through a Falk Medical Research Transformational Award (to M.M.). M.M. is a Howard Hughes Medical Institute (HHMI) Faculty Scholar. Author contributions: H.Q. designed the project, oversaw the experiments, analyzed the data, and wrote the manuscript. Z.D., F.W., W.X., and H.S. conducted the in vitro and in vivo experiments. X.W. and M.W. developed and conducted the CAR T cell degranulation and activation assays. W.A.C. and D.L.S. contributed to the data analysis and manuscript preparation. G.W. and X.S. developed the BAFF-R scFv. F.F. and J.X. developed and conducted the surface antigen density assays. T.I.P., C.-W.C., C.K., L.S., and G.G.I. developed the PDX models. J.Y.S. and I.A. provided the primary tumor samples. M.M., S.J.F., and L.W.K. oversaw the project including the data analysis and manuscript writing. Competing interests: L.W.K. and H.Q. are inventors on patents WO2017214167 and WO 2017214170, submitted by the City of Hope, which is related to this work. L.W.K.: InnoLifes, consultancy and equity ownership; Pepromene Bio, consultancy and equity ownership. H.Q.: InnoLifes, consultancy and equity ownership; Pepromene Bio, consultancy and equity ownership. The other authors declare that they do not have competing interests. Data and materials availability: All data associated with this study are present in the paper or Supplementary Materials. Materials produced in this study are protected by the City of Hope intellectual property patents but will remain available to qualified investigators at other research organizations by establishing a material transfer agreement and in accordance with the NIH principles and guidelines. The following reagents are available from Larry Kwak under a material transfer agreement with the Beckman Research Institute of the City of Hope, subject to third party rights. Reagents: BAFF-R CAR T cells, BAFF-R CAR vector plasmid, JeKo-1-Luciferase, Raji-Luciferase, Z-138-Luciferase, Z-138-Luciferase-CD19KO, MEC-1-CD19KO, Nalm6-Luciferase, and Nalm6-Luciferase-CD19KO.

Authors

Affiliations

Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Xiuli Wang
Center for CAR T Cell Therapy, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Wesley A. Cheng
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Department of Medical Oncology Cancer Center, West China Hospital, Sichuan University, Sichuan 910041, China.
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China.
Han Sun
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Center for CAR T Cell Therapy, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Guowei Wei
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
D. Lynne Smith
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Xiuhua Sun
The Second Affiliated Hospital of Dalian Medical University, Dalian 116044, China.
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, CA 90007, USA.
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, CA 90007, USA.
Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Joo Y. Song
Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Ibrahim Aldoss
Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Clarisse Kayembe
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Luisa Sarno
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Markus Müschen
Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Giorgio G. Inghirami
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Stephen J. Forman
Center for CAR T Cell Therapy, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

Funding Information

Notes

*
These authors contributed equally to this work.
†Corresponding author. Email: [email protected]

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  10. The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma, Cancer Immunology Research, 9, 1, (75-88), (2020).https://doi.org/10.1158/2326-6066.CIR-20-0236
    Crossref
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