Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Ding, Lijuan; Wang, Yiyun; Hong, Ruoxi; Zhao, Houli; Zhou, Linghui; Wei, Guoqing; Wu, Wenjun; Xu, Huijun; Zhang, Yanlei; Luo, Yi; Shi, Jimin; Chang, Alex H.; Hu, Yongxian; Huang, He

doi:10.3389/fonc.2021.750218

Cited by 11 publications

(13 citation statements)

References 36 publications

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“…CAR-T infusions post-allo-HCT have been intensively investigated, especially in B-ALL. Both allogenic and autologous CAR-T cells targeting CD19 (CART19) have been applied in clinical trials for B-ALL relapse after allo-HCT, with a CR rate of more than 80% (145) (146,147). Apart from the satisfactory remission rate, CAR-T seems to confer a lower aGVHD incidence compared to DLI.…”

Section: Car-t and Car-nk Cellsmentioning

confidence: 99%

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection (e.g., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy.

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Section: Car-t and Car-nk Cellsmentioning

confidence: 99%

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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“…Second, the efficacy of CAR-T for B-ALL relapsed following allo-HSCT is related to the HLA disparity between the donor and recipient. In one retrospective study of 20 R/R B-ALL patients with post-transplant relapse, CR rates following allogeneic CAR-T cells and autologous CAR-T cells in the HLA-matched transplantation group and haploidentical transplantation group were 100% (3/3), 100% (4/4), 87.5% (7/8), and 75% (3/4), respectively [39].…”

Section: The Efficacy Of Cd19 Car-t For B-all Relapsed After Allo-hsc...mentioning

confidence: 99%

“…Patients who received haploidentical donor-derived CAR-T cells were more likely to develop aGVHD compared to those that received sibling-identical donor-derived CAR-T cells according to one study [39]. In a study from the Tianjin First Center Hospital in China, 6 of 9 (66.7%) patients who received haploidentical donor-derived CAR-T cells developed aGVHD, including 4 grade III-IV aGVHD.…”

Section: Graft-versus-host Disease After Car-t Cell Therapy For B-all...mentioning

confidence: 99%

“…Based on limited data, the principles of GVHD treatment following CAR-T are the same as those of GVHD after allo-HSCT [28,39,64]. Patients with symptoms of aGVHD can be effectively controlled with immunosuppressants, which include methylprednisolone, cyclosporine, tacrolimus, anti-CD25 monoclonal antibody, and ruxolitinib [28,39,64].…”

Section: Graft-versus-host Disease After Car-t Cell Therapy For B-all...mentioning

confidence: 99%

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Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation

Cao

2022

Int J Hematol

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for B-cell acute lymphoblastic leukemia (B-ALL). Although allo-HSCT can be curative for some B-ALL patients, relapse still occurs in some patients following allo-HSCT. Conventional chemotherapies show poor efficacy in B-ALL patients who have relapsed following allo-HSCT. In the past decade, chimeric antigen receptor T-cell (CAR-T) therapy has shown to be efficacious for B-ALL patients. In particular, autologous CD19 CAR-T therapy results in a high remission rate. However, there are challenges in the use of CD19 CAR-T therapy for B-ALL patients who have relapsed following allo-HSCT, including the selection of CAR-T cell source for manufacturing, post-CAR-T graft-versus-host disease (GVHD) risk, maintenance of long-term efficacy after remission through CAR-T therapy, and whether a consolidative second transplant is needed. In this review, we describe the current status of CAR-T therapy for B-ALL patients who have relapsed following allo-HSCT, the advantages and disadvantages of various CAR-T cell sources, the characteristics and management of GVHD following CAR-T therapy, and the risk factors that may affect long-term efficacy. Keywords Allogeneic hematopoietic stem cell transplantation • CD19 chimeric antigen receptor T-cell therapy • B-cell acute lymphoblastic leukemia • Relapse Prevention and management of relapse after allogeneic hematopoietic cell transplantation in hematological malignanciesPei-hua Lu and Kai-yan Liu have contributed equally to this work.

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“…CAR T cell therapy has seen the most promising clinical responses against tumors of the B cell lineages [ 10 , 11 , 12 ], which also led to the first ever approved cellular therapy for cancer and first ever approved gene therapy by the U.S. Food and Drug Administration (FDA) [ 13 ]. Thus far, five CAR T cell therapies have gone through FDA approval, targeting B cell leukemia [ 13 , 14 ], lymphoma [ 15 , 16 ], and multiple myeloma [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Xiao

Brown

et al. 2022

IJMS

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Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.

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Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Cited by 11 publications

References 36 publications

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

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