Chimeric antigen receptor T cells: a novel therapy for solid tumors

Yu, Shengnan; Li, An‐Ping; Liu, Qian; Li, Tengfei; Yuan, Xun; Han, Xinwei; Wu, Kongming

doi:10.1186/s13045-017-0444-9

Cited by 252 publications

(190 citation statements)

References 139 publications

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“…Early clinical trials that investigated anti-CD19 CAR-T cells in hematologic malignancies have demonstrated continued remission in patients with late stage disease [1][2][3][4][5]. CAR-T cell therapy investigating different cancer-specific targets have also shown some potential in studies of non-hematopoietic malignancies [6]. These promising results have been tempered by safety considerations, including cytokine release syndrome, neurotoxicity, and other rare and uncommon adverse events [7,8].…”

mentioning

confidence: 99%

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

140

122

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Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception -November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy. (M.M. Lalu). @manojlalu (M.M. Lalu).

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mentioning

confidence: 99%

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

140

122

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“…Trials are currently underway to assess the safety and efficacy of CARs in the treatment of glioblastoma, mesothelioma, and breast and ovarian carcinoma. 10,30 At the time of article preparation, several hundred active clinical trials involving CAR T-cell therapy are registered on ClinicalTrials.gov. An abundance of clinical data is thus likely to emerge in the coming months to years.…”

Section: Outcomes To Date From Car T-cell Therapymentioning

confidence: 99%

“…CD8+ CAR T-cells also exert cytotoxic effects by releasing granzyme and perforin granules, and directly stimulating apoptosis via first apoptosis signal and its ligand (fas/fas-L) and tumor necrosis factor (TNF)/TNF receptor (TNF-R) pathways that lead to tumor cell destruction. 10 Identifying suitable tumor targets is a key aspect of CAR construction. An ideal target antigen is abundantly present at the surface of tumor cells and only minimally present or absent in healthy tissue to mitigate nontumor effects.…”

mentioning

confidence: 99%

Next Generation of Cancer Treatments: Chimeric Antigen Receptor T-Cell Therapy and Its Related Toxicities: A Review for Perioperative Physicians

Echeverry

Fischer

Mead

2019

Anesthesia &Amp; Analgesia

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Cancer immunotherapy has entered a new era with the recent introduction of genetically engineered T-cells that express chimeric antigen receptors (CARs) capable of recognizing and destroying tumor cells. Several clinical trials in patients with relapsed or refractory B-cell malignancies have demonstrated complete remission rates ranging from 50% to 90%, with long-term data suggestive of a possible curative response. CAR T-cell therapy is currently under investigation for earlier use in these disease processes and in various other solid and liquid tumors. CAR T-cell therapy is associated with a unique postinfusion toxicity profile including cytokine-release syndrome and neurotoxicity. These toxicities are usually reversible but can be fatal, requiring close vigilance and prompt treatment often in an intensive care unit (ICU) setting. CAR T-cell therapy is currently restricted to designated centers possessing expertise in acute toxicity management, but wider use is likely if early therapeutic successes are replicated. As perioperative and critical care physicians, anesthesiologists may encounter such patients in the perioperative or ICU setting and should become familiar with this unique and novel therapeutic modality capable of causing extreme cardiovascular and respiratory compromise. This review will describe the immunobiology of CAR T-cells, their relevance to cancer treatment, clinical aspects of their therapeutic use in cancer chemotherapy, toxicities related to CAR T-cell use, and their therapeutic management.

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“…The past decades have witnessed the great progress in developing novel effective therapies [9–12], especially through diverting tumor cells from a proliferation phenotype towards a non-division state. Among the emerging therapies, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are the most attractive findings.…”

Section: Introductionmentioning

confidence: 99%

Recent advances of highly selective CDK4/6 inhibitors in breast cancer

Liu

et al. 2017

J Hematol Oncol

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130

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Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Food and Drug Administration has approved palbociclib and ribociclib for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer, and recent clinical trial data suggest that palbociclib significantly improved clinical outcome when combined with letrozole or fulvestrant. Besides, the favorable effects of abemaciclib on prolonging survival of breast cancer patients have also been observed in clinical trials both for single-agent and combination strategy. In this review, we outline the preclinical and clinical advancement of these three orally bioavailable and highly selective CDK4/6 inhibitors in breast cancer.

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Chimeric antigen receptor T cells: a novel therapy for solid tumors

Cited by 252 publications

References 139 publications

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Next Generation of Cancer Treatments: Chimeric Antigen Receptor T-Cell Therapy and Its Related Toxicities: A Review for Perioperative Physicians

Recent advances of highly selective CDK4/6 inhibitors in breast cancer

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