Current Progress in CAR-T Cell Therapy for Hematological Malignancies

Han, Donglei; Xu, Zenghui; Zhuang, Yuan; Ye, Zhenlong; Qian, Qijun

doi:10.7150/jca.48976

Cited by 131 publications

(88 citation statements)

References 48 publications

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“…Activation of TLR3-promoted apoptosis of prostate cancer cells via PKC-alpha-dependent signaling in combinational therapy with 5-FU significantly increased apoptosis of human colon cancer cells [30,31]. The direct antitumor effect of TLR5 activation has been reported in 2 Journal of Immunology Research mouse xenografts of human breast cancer cells [32]. The same autocrine effect of TLR5 activation was also reported on glioma cells via NF-kappaB activation and NO production [33].…”

Section: Macrophagesmentioning

confidence: 58%

“…Checkpoint inhibitors such as anti-PD-1/PDL-1 and anti-CTLA4 antibodies that can treat solid cancers through activation of an antitumor immune response are now approved by regulatory organizations in Europe and the US [1]. Cell-based immunotherapies such as chimeric antigen receptor (CAR) T cells have also shown to be strikingly effective in treating refractory or relapsed hematopoietic malignancies [2]. These successful experiences showed that triggering an efficient antitumor immune response could be applied as an effective therapy for cancer.…”

Section: Introductionmentioning

confidence: 99%

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Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

Pahlavanneshan

Sayadmanesh

Ebrahimiyan

et al. 2021

Journal of Immunology Research

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Toll-like receptors (TLRs) are expressed and play multiple functional roles in a variety of immune cell types involved in tumor immunity. There are plenty of data on the pharmacological targeting of TLR signaling using agonist molecules that boost the antitumor immune response. A recent body of research has also demonstrated promising strategies for improving the cell-based immunotherapy methods by inducing TLR signaling. These strategies include systemic administration of TLR antagonist along with immune cell transfer and also genetic engineering of the immune cells using TLR signaling components to improve the function of genetically engineered immune cells such as chimeric antigen receptor-modified T cells. Here, we explore the current status of the cancer immunotherapy approaches based on manipulation of TLR signaling to provide a perspective of the underlying rationales and potential clinical applications. Altogether, reviewed publications suggest that TLRs make a potential target for the immunotherapy of cancer.

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Section: Macrophagesmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

Pahlavanneshan

Sayadmanesh

Ebrahimiyan

et al. 2021

Journal of Immunology Research

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“…In chimeric antigen receptor (CAR) T-cell therapy, T cells isolated from a patient with cancer are engineered to express tumor antigen-specific receptors that facilitate the elimination of tumor cells upon reintroduction [ 125 ]. Two CAR T-cell therapies, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), have been FDA-approved for hematological malignancies [ 126 ]. Rosenberg and others reported successful outcomes of ACT-TIL therapy in metastatic melanoma; these are thought to be partly due to the high acquired/somatic mutational load and the highly immunogenic nature of this cancer [ 122 , 123 , 124 , 125 ].…”

Section: Immunotherapymentioning

confidence: 99%

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

Singh

Yadav

2021

Biomedicines

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Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

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“…Also, there is the risk of insertional mutagenesis caused by randomly integrating viral vectors. Moreover, in case of leukemias, blood-derived T cells might be contaminated with leukemic cells (Han, Xu, Zhuang, Ye, & Qian, 2021). Therefore, there are several manufacturing challenges that can affect the quality of CAR-T cell products (Marofi et al, 2021).…”

Section: Overview Of Car-t Cellsmentioning

confidence: 99%

Strengthening the CAR-T Cell Therapeutic Application using CRISPR/Cas9 Technology

Nezhad

Yazdanifar

Abdollahpour‐Alitappeh

et al. 2021

Preprint

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Adoptive cell immunotherapy with chimeric antigen receptor (CAR) T cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, FDA approved three types of CAR-T cells against CD19 hematologic malignancies, including Tisagenlecleucel (Kymriah), Axicabtagene ciloleucel (Yescarta), and Brexucabtagene autoleucel (Tecartus). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) system has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cell’s anti-tumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be utilized to reduce CAR-T cells toxicity and side effects. Hereby, we discuss the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

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Current Progress in CAR-T Cell Therapy for Hematological Malignancies

Cited by 131 publications

References 48 publications

Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

Strengthening the CAR-T Cell Therapeutic Application using CRISPR/Cas9 Technology

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