Overcome tumor relapse in CAR T cell therapy

Huo, Cheng-Dong; Yang, Jie; Gu, Yanmei; Wang, Dai-Jun; Zhang, Xiaoxia; Li, Yumin

doi:10.1007/s12094-022-02847-2

Cited by 3 publications

(2 citation statements)

References 104 publications

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“…However, while autologous chimeric antigen receptor (CAR)-expressing T cells have rapidly become a mainstay for the treatment of various hematological malignancies [ 3 ], such an ACT variant is not yet licensed for the treatment of solid tumors, and no other forms of ACT has yet received regulatory approval for routine clinical use in cancer patients. Moreover, while > 80% of patients with hematological tumors receiving CAR-expressing T cells experience (often profound) objective responses, a sizeable proportion thereof ultimately relapse, often (but not always) due to the loss of the antigenic CAR target [ 4 , 5 ]. Thus, there is ample room for improvement in the ACT field.…”

Section: Introductionmentioning

confidence: 99%

NK cells and solid tumors: therapeutic potential and persisting obstacles

et al. 2022

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Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity.

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Section: Introductionmentioning

confidence: 99%

NK cells and solid tumors: therapeutic potential and persisting obstacles

et al. 2022

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“…20 Their findings show that the absence of accessory proteins would interfere with the normal surface expression of target antigens on tumor cells (Figure 3c). 20,21 However, this is not the only mechanism of immune escape from tumor cells, as Evans et al first reported a case of a relapsed, refractory chronic lymphocytic leukemia (CLL) patient treated with CD19 protein-based CAR-T cells who later relapsed to CD19-negative plasmacytoid lymphoma (Figure 3d). 22 Moreover, Jacoby et al reported that CARinduced immunological stress on CD19 led to a variety of leukemic changes.…”

Section: Loss Of Target Antigenmentioning

confidence: 99%

Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells

Hu,

Yang,

Wang

et al. 2024

IJN

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Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach. In this review, we present CAR-T cell-based therapies for the treatment of tumors, including the features and benefits of CAR-T therapies, the limitations that exist in this field, and the measures taken to overcome them. Furthermore, we discuss the notable benefits of utilizing exosomes released from CAR-T cells in tumor treatment and anticipate potential issues in clinical trials. Lastly, drawing from previous research on exosomes from CAR-T cells and the characteristics of exosomes, we propose strategies to overcome these restrictions. Additionally, the review discusses the plight in large-scale preparation of exosome and provides potential solutions for future clinical applications.

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