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Citations to this article

Clinical and immunological responses after CD30-specific chimeric antigen receptor–redirected lymphocytes
Carlos A. Ramos, … , Gianpietro Dotti, Barbara Savoldo
Carlos A. Ramos, … , Gianpietro Dotti, Barbara Savoldo
Published August 14, 2017
Citation Information: J Clin Invest. 2017;127(9):3462-3471. https://doi.org/10.1172/JCI94306.
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Clinical Research and Public Health Article has an altmetric score of 74

Clinical and immunological responses after CD30-specific chimeric antigen receptor–redirected lymphocytes

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Abstract

BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being treated with brentuximab. RESULTS. No toxicities attributable to CD30.CAR-Ts were observed. Of 7 patients with relapsed HL, 1 entered complete response (CR) lasting more than 2.5 years after the second infusion of CD30.CAR-Ts, 1 remained in continued CR for almost 2 years, and 3 had transient stable disease. Of 2 patients with ALCL, 1 had a CR that persisted 9 months after the fourth infusion of CD30.CAR-Ts. CD30.CAR-T expansion in peripheral blood peaked 1 week after infusion, and CD30.CAR-Ts remained detectable for over 6 weeks. Although CD30 may also be expressed by normal activated T cells, no patients developed impaired virus-specific immunity. CONCLUSION. CD30.CAR-Ts are safe and can lead to clinical responses in patients with HL and ALCL, indicating that further assessment of this therapy is warranted. TRIAL REGISTRATION. ClinicalTrials.gov NCT01316146. FUNDING. National Cancer Institute (3P50CA126752, R01CA131027 and P30CA125123), National Heart, Lung, and Blood Institute (R01HL114564), and Leukemia and Lymphoma Society (LLSTR 6227-08).

Authors

Carlos A. Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P. Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M. Bollard, Bill H. Chang, Cliona M. Rooney, Malcolm K. Brenner, Helen E. Heslop, Gianpietro Dotti, Barbara Savoldo

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M Castella, M Caballero-Baños, V Ortiz-Maldonado, EA González-Navarro, G Suñé, A Antoñana-Vidósola, A Boronat, B Marzal, L Millán, B Martín-Antonio, J Cid, M Lozano, E García, J Tabera, E Trias, U Perpiña, JM Canals, T Baumann, D Benítez-Ribas, E Campo, J Yagüe, Á Urbano-Ispizua, S Rives, J Delgado, M Juan
Frontiers in immunology 2020
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice
M Cerrano, M Ruella, MA Perales, C Vitale, DG Faraci, L Giaccone, M Coscia, M Maloy, M Sanchez-Escamilla, H Elsabah, A Fadul, E Maffini, G Pittari, B Bruno
Frontiers in immunology 2020
Clinical CAR-T Cell and Oncolytic Virotherapy for Cancer Treatment
N Watanabe, MK McKenna, AR Shaw, M Suzuki
Molecular Therapy 2020
Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress
J Zhao, M Wu, Z Li, S Su, Y Wen, L Zhang, Y Li
Annals of Hematology 2020
The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy
D Liu, S Badeti, G Dotti, JJ, H Wang, J Dermody, P Soteropoulos, D Streck, RB Birge, C Liu
Cell Communication and Signaling 2020
Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies
WY Lin, HH Wang, YW Chen, CF Lin, HC Fan, YY Lee
International journal of molecular sciences 2020
Overcoming Heterogeneity of Antigen Expression for Effective CAR T Cell Targeting of Cancers
S Kailayangiri, B Altvater, M Wiebel, S Jamitzky, C Rossig
Cancers 2020
Cellular Immunotherapy in Lymphoma: Beyond CART Cells
MR Gaballa, CA Ramos
Current Treatment Options in Oncology 2020
Engineered off-the-shelf therapeutic T cells resist host immune rejection
F Mo, N Watanabe, MK McKenna, MJ Hicks, M Srinivasan, D Gomes-Silva, E Atilla, T Smith, PA Atilla, R Ma, D Quach, HE Heslop, MK Brenner, M Mamonkin
Nature Biotechnology 2020
A Bird’s-Eye View of Cell Sources for Cell-Based Therapies in Blood Cancers
B Motais, S Charvátová, M Hrdinka, M Šimíček, T Jelínek, T Ševčíková, Z Kořístek, R Hájek, JR Bagó
Cancers 2020
A novel chimeric antigen receptor redirecting T-cell specificity towards CD26+ cancer cells
S Zhou, W Li, Y Xiao, X Zhu, Z Zhong, Q Li, F Cheng, P Zou, Y You, X Zhu
Leukemia 2020
Hematopoietic Cell Transplantation and Adoptive Cell Therapy in Peripheral T Cell Lymphoma
AM Rogers, JE Brammer
Current Hematologic Malignancy Reports 2020
Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy
MS Thakar, TJ Kearl, S Malarkannan
Frontiers in Oncology 2020
Adoptive T cell therapy: Boosting the immune system to fight cancer
E Leon, R Ranganathan, B Savoldo
Seminars in Immunology 2020
CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells
M Guercio, D Orlando, SD Cecca, M Sinibaldi, I Boffa, S Caruso, Z Abbaszadeh, A Camera, B Cembrola, K Bovetti, S Manni, I Caruana, R Ciccone, FD Bufalo, P Merli, L Vinti, K Girardi, A Ruggeri, CD Stefanis, M Pezzullo, E Giorda, M Scarsella, RD Vito, S Barresi, A Ciolfi, M Tartaglia, L Moretta, F Locatelli, C Quintarelli, BD Angelis
Haematologica 2020
Advances in targeted therapy for malignant lymphoma
L Wang, W Qin, YJ Huo, X Li, Q Shi, JE Rasko, A Janin, WL Zhao
Signal Transduction and Targeted Therapy 2020
Cytokines in CAR T Cell–Associated Neurotoxicity
J Gust, R Ponce, WC Liles, GA Garden, CJ Turtle
Frontiers in immunology 2020
Hodgkin lymphoma
JM Connors, W Cozen, C Steidl, A Carbone, RT Hoppe, HH Flechtner, NL Bartlett
Nature Reviews Disease Primers 2020
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma
CA Ramos, NS Grover, AW Beaven, PD Lulla, MF Wu, A Ivanova, T Wang, TC Shea, CM Rooney, C Dittus, SI Park, AP Gee, PW Eldridge, KL McKay, B Mehta, CJ Cheng, FB Buchanan, BJ Grilley, K Morrison, MK Brenner, JS Serody, G Dotti, HE Heslop, B Savoldo
Journal of Clinical Oncology 2020
Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia
F Bayón-Calderón, ML Toribio, S González-García
International journal of molecular sciences 2020
A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma
H Zhao, Y Wang, ET Yin, K Zhao, Y Hu, H Huang
Frontiers of Medicine 2020
GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision
K Wang, Y Chen, S Ahn, M Zheng, E Landoni, G Dotti, B Savoldo, Z Han
2020
Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy
AV de Jonge, T Mutis, MG Roemer, B Scheijen, ME Chamuleau
Cancers 2020
Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies
W Yan, Z Liu, J Liu, Y Xia, K Hu, J Yu, YQ Li
BioMed Research International 2020
Peripheral T cell lymphomas: from the bench to the clinic
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Nature Reviews Cancer 2020
Outcome after autologous stem cell transplantation in primary refractory or relapsed Hodgkin lymphoma—a long-term follow-up single center experience
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Annals of Hematology 2020
The role of trogocytosis in immune surveillance of Hodgkin lymphoma
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OncoImmunology 2020
Non-signaling Chimeric Antigen Receptors Enhance Antigen-Directed Killing by γδ T Cells in Contrast to αβ T Cells
LC Fleischer, SA Becker, RE Ryan, A Fedanov, CB Doering, HT Spencer
Molecular Therapy — Oncolytics 2020
Treatment approaches in relapsed or refractory peripheral T-cell lymphomas
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F1000Research 2020
Fungal Infections Associated With the Use of Novel Immunotherapeutic Agents
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Current Clinical Microbiology Reports 2020
Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy
TJ Voorhees, N Ghosh, N Grover, J Block, C Cheng, K Morrison, A Ivanova, G Dotti, J Serody, B Savoldo, AW Beaven
Blood Advances 2020
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma
SS Neelapu, S Adkins, SM Ansell, J Brody, MS Cairo, JW Friedberg, JP Kline, R Levy, DL Porter, K van Besien, M Werner, MR Bishop
Journal for ImmunoTherapy of Cancer 2020
A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families
J Wang, K Urbanska, P Sharma, R Nejati, L Shaw, MS Lim, SJ Schuster, DJ Powell
Human vaccines 2020
B7-H3 Chimeric Antigen Receptor Redirected T Cells Target Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma
Z Zi, H Zhao, H Wang, X Ma, F Wei
Cancers 2020
Quantitative PCR methodology with a volume-based unit for the sophisticated cellular kinetic evaluation of chimeric antigen receptor T cells
S Yamamoto, S Matsumoto, A Goto, M Ugajin, M Nakayama, Y Moriya, H Hirabayashi
Scientific Reports 2020
Antitumor Effects of CAR T Cells Redirected to the EDB Splice Variant of Fibronectin
J Wagner, E Wickman, TI Shaw, AA Anido, D Langfitt, J Zhang, SN Porter, SM Pruett-Miller, H Tillman, G Krenciute, S Gottschalk
Cancer immunology research 2020
Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma
TJ Voorhees, AW Beaven
Cancers 2020
Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients
D Wang, C Zeng, B Xu, JH Xu, J Wang, LJ Jiang, QX Wang, CR Li, N Wang, L Huang, YC Zhang, Y Xiao, JF Zhou
Blood Cancer Journal 2020
Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma
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Experimental Hematology and Oncology 2020
Therapy of Peripheral T Cell Lymphoma: Focus on Nodal Subtypes
PB Allen, B Pro
Current Oncology Reports 2020
Pembrolizumab (and friends) in pediatric malignancies: should we consider Hodgkin lymphoma a world of its own?
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Annals of translational medicine 2020
Harnessing immunotherapy for pediatric T-cell malignancies
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Expert Review of Clinical Immunology 2020
T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy
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Journal of Clinical Investigation 2019
Novel insights into the role of aptamers in the fight against cancer
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Journal of Cancer Research and Clinical Oncology 2019
CAR‐T cell therapy for non‐Hodgkin lymphomas: A new treatment paradigm
LQ Hill, P Lulla, HE Heslop
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Genetically engineered T cells for cancer immunotherapy
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Signal Transduction and Targeted Therapy 2019
Cancer Immunotherapy with T Cells Carrying Bispecific Receptors That Mimic Antibodies
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Cancer immunology research 2019
Beyond CAR T Cells: Other Cell-Based Immunotherapeutic Strategies Against Cancer
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Frontiers in Oncology 2019
Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions
LC Fleischer, HT Spencer, SS Raikar
Journal of Hematology & Oncology 2019
Challenges of driving CD30-directed CAR-T cells to the clinic
NS Grover, B Savoldo
BMC Cancer 2019
Chimeric Antigen Receptor–Engineered T Cell Therapy in Lymphoma
P Strati, SS Neelapu
Current Oncology Reports 2019
Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety—A Systematic Review with Meta-Analysis
WL Yu, ZC Hua
Cancers 2019
Chimeric Antigen Receptors for T-Cell Malignancies
LD Scherer, MK Brenner, M Mamonkin
Frontiers in Oncology 2019
Engineered T Cell Therapy for Cancer in the Clinic
L Zhao, YJ Cao
Frontiers in immunology 2019
Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment
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Current Treatment Options in Neurology 2019
Current status and hurdles for CAR-T cell immune therapy
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Current advances in Hodgkin’s lymphoma
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Chronic Diseases and Translational Medicine 2019
Genetically engineered CAR T-immune cells for cancer therapy: recent clinical developments, challenges, and future directions
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Journal of Applied Biomedicine 2019
CAR-Based Approaches to Cutaneous T-Cell Lymphoma
I Scarfò, MJ Frigault, MV Maus
Frontiers in Oncology 2019
Evaluating the effects of design parameters on the performances of phase I trial designs
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Contemporary Clinical Trials Communications 2019
Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy
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Cancers 2019
Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies
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Cancers 2019
Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin’s Lymphoma
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Molecular Therapy — Oncolytics 2019
Blocking CD30 on T Cells by a Dual Specific CAR for CD30 and Colon Cancer Antigens Improves the CAR T Cell Response against CD30− Tumors
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Molecular Therapy 2019
CAR T Cell Therapy for Hematological Malignancies
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CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30+ and CD30- Embryonal Carcinoma via Antigen-dependent and Fas/FasL Interactions
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Cancer immunology research 2018
Chimeric antigen receptor T‑cell therapy—a hematological success story
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CAR-T cell therapy, a door is open to find innumerable possibilities of treatments for cancer patients
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Blood 2018
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Blood 2018
How to Hit Mesenchymal Stromal Cells and Make the Tumor Microenvironment Immunostimulant Rather Than Immunosuppressive
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Frontiers in immunology 2018
Immune Response against ALK in Children with ALK-Positive Anaplastic Large Cell Lymphoma
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Cancers 2018
Novel Immunotherapies for T Cell Lymphoma and Leukemia
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Current Hematologic Malignancy Reports 2018
Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas
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Cancers 2018
Absence of Replication-Competent Retrovirus in Vectors, T Cell Products, and Patient Follow-Up Samples
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Blood Reviews 2018
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Current Status of Gene Engineering Cell Therapeutics
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Frontiers in immunology 2018
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Blood 2018
Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma
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Nature 2018
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F1000Research 2018
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