CAR T-cell immunotherapy of B-cell malignancy: the story so far

Halim, Leena; Maher, John

doi:10.1177/2515135520927164

Cited by 42 publications

(32 citation statements)

References 93 publications

(136 reference statements)

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“…In another study, pharmacological blocking of HSP90 resulted in decreased expression of Linker FIGURE 2 | HSPs and CAR T/NK cells in lymphoma immunotherapy. Chimeric Antigens Receptor (CAR) targeting CD19 and CD30 showed promising results in patients with r/r lymphoma (93,129,131,132). Autologous NK cells pre-activated with cytokines (IL-2, IL-15) and 14-mer HSP70-derived peptide (TKD) can be used for ex vivo activation of NK cells for the adoptive transfer therapy (137)(138)(139)(140).…”

Section: Hsps and Emerging Lymphoma Immunotherapymentioning

confidence: 99%

Heat Shock Proteins in Lymphoma Immunotherapy

2021

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Immunotherapy harnessing the host immune system for tumor destruction revolutionized oncology research and advanced treatment strategies for lymphoma patients. Lymphoma is a heterogeneous group of cancer, where the central roles in pathogenesis play immune evasion and dysregulation of multiple signaling pathways. Immunotherapy-based approaches such as engineered T cells (CAR T), immune checkpoint modulators and NK cell-based therapies are now in the frontline of lymphoma research. Even though emerging immunotherapies showed promising results in treating lymphoma patients, low efficacy and on-target/off-tumor toxicity are of a major concern. To address that issue it is suggested to look into the emerging role of heat shock proteins. Heat shock proteins (HSPs) showed to be highly expressed in lymphoma cells. HSPs are known for their abilities to modulate immune responses and inhibit apoptosis, which made their successful entry into cancer clinical trials. Here, we explore the role of HSPs in Hodgkin and Non-Hodgkin lymphoma and their involvement in CAR T therapy, checkpoint blockade and NK cell- based therapies. Understanding the role of HSPs in lymphoma pathogenesis and the ways how HSPs may enhance anti-tumor responses, may help in the development of more effective, specific and safe immunotherapy.

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Section: Hsps and Emerging Lymphoma Immunotherapymentioning

confidence: 99%

Heat Shock Proteins in Lymphoma Immunotherapy

2021

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“…This form of therapy utilizes genetic engineering to create CAR that possess antigen-specific extracellular domains tethered to intracellular signaling domains that, upon recognition of a tumor associated antigen, can activate downstream signaling pathways to kill tumor cells [ 57 ]. Thus far, CAR T cells have proven to be effective in the setting of relapsed/refractory, CD19-expressing B cell malignancies such as acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL) [ 58 ]. However, the use of CAR T cells has yet to be widely effective against AML, likely due to the heterogeneity of the disease, narrow therapeutic window, side effects of CAR T therapy, and the difficulty in identifying a common surface antigen to target [ 59 ].…”

Section: Nk Cell Therapies In Amlmentioning

confidence: 99%

Unraveling the Role of Innate Lymphoid Cells in Acute Myeloid Leukemia

Lordo

Scoville

Goel

et al. 2021

Cancers

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Over the past 50 years, few therapeutic advances have been made in treating acute myeloid leukemia (AML), an aggressive form of blood cancer, despite vast improvements in our ability to classify the disease. Emerging evidence suggests the immune system is important in controlling AML progression and in determining prognosis. Natural killer (NK) cells are important cytotoxic effector cells of the innate lymphoid cell (ILC) family that have been shown to have potent anti-leukemic functions. Recent studies are now revealing impairment or dysregulation of other ILCs in various types of cancers, including AML, which limits the effectiveness of NK cells in controlling cancer progression. NK cell development and function are inhibited in AML patients, which results in worse clinical outcomes; however, the specific roles of other ILC populations in AML are just now beginning to be unraveled. In this review, we summarize what is known about the role of ILC populations in AML.

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“…Chimeric antigen receptor T cells (CAR-T) are T cells expressing artificial T cell receptors which contain both tumor specificas well as T cell activating motifs (59). Promising results from clinical trials had led to several CAR-T cell therapies approved by the United States Food and Drug Administration and European Medicines Agency for treating relapsed or refractory B cell malignancies (60). In spite of the similarity between chimeric antigen receptors (CARs) and natural TCRs, reduced efficiency of antigen-recognition and affinity remain major issues in CAR-T cell therapies.…”

Section: Car-t Cellsmentioning

confidence: 99%

ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies

2020

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Zeta-chain-associated protein kinase-70 (ZAP-70) is a tyrosine kinase mainly expressed in T cells, NK cells and a subset of B cells. Primarily it functions in T cell receptor (TCR) activation through its tyrosine kinase activity. Aberrant expression of ZAP-70 has been evidenced in different B cell malignancies, with high expression of ZAP-70 in a subset of patients with Chronic Lymphocytic Leukemia (CLL), associating with unfavorable disease outcomes. Previous studies to understand the mechanisms underlying this correlation have been focused on tumor intrinsic mechanisms, including the activation of B cell receptor (BCR) signaling. Recent evidence also suggests that ZAP-70, intrinsically expressed in tumor cells, can modulate the cross-talk between malignant B cells and the immune environment, implying a more complex role of ZAP-70 in the pathogenesis of B cell malignancies. Meanwhile, the indispensible roles of ZAP-70 in T cell and NK cell activation also demonstrate that the autologous expression of ZAP-70 in the immune environment can be a central target in modulation of tumor immunity. Here we review the evidences of the link between ZAP-70 and tumor immunology in the microenvironment in B cell malignancies. Considering an emerging role of immunotherapies in treating these conditions, understanding the distinct molecular functions of ZAP-70 in a broader cellular context could ultimately benefit patient care.

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CAR T-cell immunotherapy of B-cell malignancy: the story so far

Cited by 42 publications

References 93 publications

Heat Shock Proteins in Lymphoma Immunotherapy

Heat Shock Proteins in Lymphoma Immunotherapy

Unraveling the Role of Innate Lymphoid Cells in Acute Myeloid Leukemia

ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies

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