A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy

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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“…The B-cell aplasia persistence ranged from 1 month to 4 years among these studies [3,22,23,26,46,80].…”

Section: Resultsmentioning

confidence: 88%

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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“…Despite the promising clinical results, CAR-T cell therapy also involves several deleterious types of toxicity due to the inability to control T cell activity and some tumor-associated antigens that are presented by both diseased and healthy tissue. The prominent toxicity of CAR-T cell therapy involves cytokine release syndrome (CRS) and "on-target, offtumor" toxicity [11].…”

Section: Chimeric Antigen Receptor T-cell Therapy(car-t Cell Therapy)mentioning

confidence: 99%

Nanomedicine - the Future of Cancer Treatment: A Review

Sebastian¹

2017

JCPCR

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Conventional cancer therapies are limited to surgery, radiation, and chemotherapy. Conventional treatments come with significant adverse effects. Modern cancer treatments focus on precise drug delivery to the cancer tissues and minimize adverse effects on healthy cells. Researchers have been working on an improved technique for delivering chemotherapeutic agents precisely at the molecular level in the tumor tissue. It has led to the use of nanotechnology in cancer treatment. Nanotechnology is the science and engineering of controlling matter, at the molecular scale, to create devices with novel chemical, physical and biological properties. Nanoscale objects are used themselves or as part of larger devices containing multiple nanoscale objects. Almost every field of Biosciences uses nanotechnology and all of which have an impact on biomedicine. It has the potential to change the current methods to diagnose and treat cancer. There has been real progress in translating nano-based cancer therapies and diagnostics into the clinic, and much more are in development. Nanoparticles are mainly used as nanocarriers to deliver the cytotoxic drugs to the tumor tissue. Use of nanoparticles is based on different concepts of pharmacology. Nanomedicine also is utilized to deliver multiple drugs at the cancer site at the same time for a better cytotoxic effect. CytImmune Sciences is a developing field of nanomedicine for targeted chemotherapy method. They selectively deliver the drug at the cancer site because of the increased permeability of the blood vessels at the tumor site. This article reviews various nanomedicine-based cancer therapeutics.

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“…The potential limitation that make a CAR-T therapy ineffective in some groups of patients is the lack of the antigens that would be specific only for leukemia cells and their ability to downregulate the antigens by the neoplastic cells, but also unsatisfactory persistence of CAR-T cells after an adoptive transfer and predominance of an immunosuppressive microenvironment, which is a result of leukemia and the host immune system interactions [36].…”

Section: To Enhance the Cytotoxic Effect: Potential Therapies Are Promentioning

confidence: 99%

Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

Barełkowska¹,

Derwich²

2017

Unique Aspects of Anti-Cancer Drug Development

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The last decade became the renaissance for investigating and exploring the potential role of immunotherapy in pediatric acute leukemia (AL). It is beyond question that there is an interaction between innate immune system and hematological malignancy. Leukemia cells inhibit the host immune response according to multiple mechanisms, but exploiting the innate immune system mechanisms can overcome the resistance to the conventional treatment. What is the role of immunotherapy in pediatric AL treatment? Does it have the potential to substitute or combine the standard chemotherapy? What is the best possible timing to take advantage of immune interventions? This review is considered to follow through the possible treatment options including their foundation, strong and weak points, but also information about possible implementation into the clinical practice.

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A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy

Cited by 247 publications

References 96 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

Nanomedicine - the Future of Cancer Treatment: A Review

Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

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