scholarly journals CAR-T-Zell-Therapie beim multiplen Myelom

Der Internist ◽  
2021 ◽  
Author(s):  
X. Zhou ◽  
H. Einsele ◽  
S. Danhof
Keyword(s):  
B Cell ◽  
Cell Maturation ◽  
Chimärer Antigenrezeptor ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

ZusammenfassungDie Behandlung mit CAR-T-Zellen (CAR chimärer Antigenrezeptor) ist eine neuartige Strategie der zellulären Immuntherapie, die das patienteneigene Immunsystem als „Waffe gegen Tumorzellen“ benutzt. Bei Patienten mit multiplem Myelom werden CAR-T-Zell-Therapien im Rahmen klinischer Studien getestet. Die aktuellen Studiendaten der gegen das „B-cell maturation antigen“ (BCMA) gerichteten CAR-T-Zell-Therapien zeigen eine beachtliche Wirksamkeit, die eine baldige Zulassung erwarten lässt. Allerdings erleiden weiterhin die meisten Patienten nach einer Behandlung mit CAR-T-Zellen ein Rezidiv. Hinzu kommt, dass CAR-T-Zell-Therapien zu schwerwiegenden Nebenwirkungen wie Zytokinfreisetzungssyndrom und Neurotoxizität mit teilweise auch letalem Ausgang führen können. Ein angemessenes Kosten-Nutzen-Verhältnis der CAR-T-Zell-Therapie stellt eine weitere Herausforderung dar. Trotz dieser Limitationen erscheint die CAR-T-Zell-Therapie eine attraktive Option für Patienten mit Myelom, sodass diese Therapie das Potenzial hat, in die Standardbehandlung integriert zu werden.

scholarly journals CAR T Cells with Enhanced Sensitivity to B Cell Maturation Antigen for the Targeting of B Cell Non-Hodgkin’s Lymphoma and Multiple Myeloma

2018 ◽  
Vol 26 (8) ◽  
pp. 1906-1920 ◽  
Author(s):  
Julia Bluhm ◽  
Elisa Kieback ◽  
Stephen F. Marino ◽  
Felix Oden ◽  
Jörg Westermann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cell ◽  
Hodgkin's Lymphoma ◽  
Cell Maturation ◽  
Car T Cells ◽  
Enhanced Sensitivity ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

scholarly journals Chimeric antigen receptor T-cell therapies for multiple myeloma

Blood ◽  
2017 ◽  
Vol 130 (24) ◽  
pp. 2594-2602 ◽  
Author(s):  
Lekha Mikkilineni ◽  
James N. Kochenderfer
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Maturation ◽  
Cell Therapies ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

Abstract Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM. Target antigens for CARs must be expressed on malignant cells, but expression on normal cells must be absent or limited. B-cell maturation antigen is expressed by normal and malignant plasma cells. CAR-Ts targeting B-cell maturation antigen have demonstrated significant antimyeloma activity in early clinical trials. Toxicities in these trials, including cytokine release syndrome, have been similar to toxicities observed in CAR-T trials for leukemia. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-Ts is a novel approach to MM therapy. MM antigens including CD138, CD38, signaling lymphocyte–activating molecule 7, and κ light chain are under investigation as CAR targets. MM is genetically and phenotypically heterogeneous, so targeting of >1 antigen might often be required for effective treatment of MM with CAR-Ts. Integration of CAR-Ts with other myeloma therapies is an important area of future research. CAR-T therapies for MM are at an early stage of development but have great promise to improve MM treatment.

scholarly journals Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma

2019 ◽  
Vol 116 (19) ◽  
pp. 9543-9551 ◽  
Author(s):  
Jie Xu ◽  
Li-Juan Chen ◽  
Shuang-Shuang Yang ◽  
Yan Sun ◽  
Wen Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cell ◽  
Cell Maturation ◽  
Durable Response ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.

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