Will allogeneic CAR T cells for CD19+ malignancies take autologous CAR T cells ‘off the shelf’?

DiNofia, Amanda M.; Grupp, Stephan A.

doi:10.1038/s41571-021-00485-1

Cited by 25 publications

(27 citation statements)

References 10 publications

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“…Rapidly evolving research advances in genomic editing methods alongside a better understanding of the mechanisms underlying the discussed toxicities will help us further prevent or manage CRS and neurotoxicity. Moving forward, having a combination of different strategies or an all-in-one unified approach for producing off-the-shelf allogeneic CAR-Ts can decrease the duration of CAR-T production and delivery and eliminate other limitations regarding the generation of autologous CAR-Ts using T cells isolated from heavily treated R/R B-ALL patients (205). A magnificent deal of effort has now been dedicated to these strategies since they can be beneficial for CAR-T therapy in both hematologic malignancies and solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

Kozani

Rahbarizadeh

2021

Front. Immunol.

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Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of ex vivo culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.

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Section: Discussionmentioning

confidence: 99%

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

Kozani

Rahbarizadeh

2021

Front. Immunol.

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“…Beyond the principle and technical factors, recently published clinical results show that autoCAR-T cells have better therapeutic efficacy than alloCAR-T cells [ 44 ]. For example, the initial overall response rate for traditional autoCAR-T(CTL-019) was reported to be approximately 90%, with a 5-year response rate reaching 58% [ 45 ].…”

Section: Strategies For Choosing a Suitable Source Of Cells For Car-t...mentioning

confidence: 99%

Strategies to enhance CAR-T persistence

Liu

Huang

et al. 2022

Biomark Res

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Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved the life expectancy for patients with refractory or relapse B cell lymphoma. As for B cell acute lymphoblastic leukemia (B-ALL), although the primary response rate is promising, the high incidence of early relapse has caused modest long-term survival with CAR-T cell alone. One of the main challenges is the limited persistence of CAR-T cells. To further optimize the clinical effects of CAR-T cells, many studies have focused on modifying the CAR structure and regulating CAR-T cell differentiation. In this review, we focus on CAR-T cell persistence and summarize the latest progress and strategies adopted during the in vitro culture stage to optimize CAR-T immunotherapy by improving long-term persistence. Such strategies include choosing a suitable cell source, improving culture conditions, combining CAR-T cells with conventional drugs, and applying genetic manipulations, all of which may improve the survival of patients with hematologic malignancies by reducing the probability of recurrence after CAR-T cell infusion and provide clues for solid tumor CAR-T cell therapy development.

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“…This represents an important issue for patients that show disease progression before CAR T-cells are available [ 62 ]. On the other hand, T-cells from healthy donors, even though not limited in numbers, could cause GVHD or be rapidly eliminated by the receptor’s immune system [ 62 , 63 ]. In any case, the use of T-cells in patients after allo-HSCT for manufacturing CAR-T opens an additional aspect of controversy.…”

Section: Autologous or Allogenic Car-tmentioning

confidence: 99%

CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

Bartoló‐Ibars

Uribe‐Herranz

Muñoz-Sánchez

et al. 2021

Cancers

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Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the standard treatments for B-cell lymphoproliferative disorders; however, deep relapses are common after an allo-HSCT, and it is associated with poor prognosis. A successful approach to overcome these relapses is to exploit the body’s own immune system with chimeric antigen receptor (CAR) T-cells. These two approaches are potentially combinatorial for treating R/R B-cell lymphoproliferative disorders. Several clinical trials have described different scenarios in which allo-HSCT and CAR-T are successively combined. Further, for all transplanted patients, assessment of chimerism is important to evaluate the engraftment success. Nonetheless, for those patients who previously received an allo-HSCT there is no monitorization of chimerism before manufacturing CAR T-cells. In this review, we focus on allo-HSCT and CAR-T treatments and the different sources of T-cells for manufacturing CAR T-cells.

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Will allogeneic CAR T cells for CD19+ malignancies take autologous CAR T cells ‘off the shelf’?

Cited by 25 publications

References 10 publications

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

Strategies to enhance CAR-T persistence

CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

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