CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy

Kim, Miriam; Cooper, Matthew; Jacobs, Michael; Ritchey, Julie; Hollaway, Julia; Fehniger, Todd A.; DiPersio, John F.

doi:10.1172/jci.insight.149819

Cited by 28 publications

(19 citation statements)

References 32 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…knocked out CD7 in hematopoietic stem cells (HSCs) and found that these CD7-KO HSCs differentiated into CD7-negative T-cells and NK cells that exhibited effector functions after transplantation into mice. This study suggests that such an approach could resolve T-cell immunodeficiency caused by CD7-CAR therapy, altogether providing a potential new approach for the development of CD7 CAR ( 85 ). In 2022, Dai et al.…”

Section: Car-t Therapy For Non-b-cell Acute Leukemiamentioning

confidence: 87%

Chimeric antigen receptor T-cell therapy for T-ALL and AML

et al. 2022

View full text Add to dashboard Cite

Non-B-cell acute leukemia is a term that encompasses T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Currently, the therapeutic effectiveness of existing treatments for refractory or relapsed (R/R) non-B-cell acute leukemia is limited. In such situations, chimeric antigen receptor (CAR)-T cell therapy may be a promising approach to treat non-B-cell acute leukemia, given its promising results in B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, fratricide, malignant contamination, T cell aplasia for T-ALL, and specific antigen selection and complex microenvironment for AML remain significant challenges in the implementation of CAR-T therapy for T-ALL and AML patients in the clinic. Therefore, designs of CAR-T cells targeting CD5 and CD7 for T-ALL and CD123, CD33, and CLL1 for AML show promising efficacy and safety profiles in clinical trials. In this review, we summarize the characteristics of non-B-cell acute leukemia, the development of CARs, the CAR targets, and their efficacy for treating non-B-cell acute leukemia.

show abstract

Section: Car-t Therapy For Non-b-cell Acute Leukemiamentioning

confidence: 87%

Chimeric antigen receptor T-cell therapy for T-ALL and AML

et al. 2022

View full text Add to dashboard Cite

show abstract

“…These CD7-KO HSCs generated functional CD7 - T cells and NK cells, although they are different from CD7 + T cells/NK cells. As the results, the mice are protected from CD7-CAR-T cell-induced immunodeficiency ( 170 ). Similarly, infusion of CD33-KO HSCs is able to restore immunity upon CD33-CAR-T cell treatment against AML ( 171 , 172 ).…”

Section: Mitigating Toxic Adverse Effects Associated With Car-t Cell ...mentioning

confidence: 87%

CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies

Huang

2022

Front. Immunol.

View full text Add to dashboard Cite

In the past decade, the emergence of chimeric antigen receptor (CAR) T-cell therapy has led to a cellular immunotherapy revolution against various cancers. Although CAR-T cell therapies have demonstrated remarkable efficacy for patients with certain B cell driven hematological malignancies, further studies are required to broaden the use of CAR-T cell therapy against other hematological malignancies. Moreover, treatment failure still occurs for a significant proportion of patients. CAR antigen loss on cancer cells is one of the most common reasons for cancer relapse. Additionally, immune evasion can arise due to the hostile immunosuppressive tumor microenvironment and the impaired CAR-T cells in vivo persistence. Other than direct antitumor activity, the adverse effects associated with CAR-T cell therapy are another major concern during treatment. As a newly emerged treatment approach, numerous novel preclinical studies have proposed different strategies to enhance the efficacy and attenuate CAR-T cell associated toxicity in recent years. The major obstacles that impede promising outcomes for patients with hematological malignancies during CAR-T cell therapy have been reviewed herein, along with recent advancements being made to surmount them.

show abstract

“…Screening for novel and specific antigens restricted to malignant cells, equipping CAR-T cells with safety switches, and post-CAR SCT may be beneficial in controlling immunodeficiency [63][64][65][66]. In addition, transplanting stem cells with deletion of target antigen genes before CAR-T cell infusion may be a promising strategy to prevent immunodeficiency [67]. All these strategies will require in-depth evaluations to validate their safety and efficacy in preclinical and clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…CD7-negative cells can tolerated well to CD7 UCAR-T cells [67]. Transplantation of gene-edited stem cells may be applied to other targets, such as CD5.…”

Section: Review Hematology and Oncology Discoverymentioning

confidence: 98%

CAR-T Cell therapy in T-cell malignancies: limitations and solutions

Shan

Feng

Pan³

2022

Hematology and Oncology Discovery

View full text Add to dashboard Cite

CD19-targeted chimeric antigen receptor (CAR)-T cell therapy has shown high potential for treating B-cell hematological malignancies and has been approved by the US FDA. However, CAR-T cell therapy for T-cell hematologic malignancies poses feasibility challenges, including the difficulty of obtaining sufficient healthy cells from patients, CAR-T cell fratricide, and the risk of immunodeficiency. In this review, we discuss bottlenecks and possible solutions in CAR-T cell therapy for T-cell acute lymphoblastic leukemias, as well as future directions in this field.

show abstract

CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy

Cited by 28 publications

References 32 publications

Chimeric antigen receptor T-cell therapy for T-ALL and AML

Chimeric antigen receptor T-cell therapy for T-ALL and AML

CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies

CAR-T Cell therapy in T-cell malignancies: limitations and solutions

Contact Info

Product

Resources

About