CRISPR/Cas9 and CAR-T cell, collaboration of two revolutionary technologies in cancer immunotherapy, an instruction for successful cancer treatment

Mollanoori, Hasan; Shahraki, Hojat; Rahmati, Yazdan; Teimourian, Shahram

doi:10.1016/j.humimm.2018.09.007

Cited by 80 publications

(49 citation statements)

References 50 publications

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“…Nowadays, there are many emerging trends in immuno-oncology, with checkpoint inhibitors, chimeric antigen T cells (CAR T-cells) and adoptive T-cell therapy (ACT) being the most promising (6). CRISPR/Cas9 gene editing technique has been used to develop CAR T-cells since 2017 (4,8,94,95). At the end of 2018 another breakthrough occurred: the direct reprogramming of mice and human fibroblasts into immune system cells, specifically, antigen-presenting dendritic cells, opening a new line of therapeutic possibilities (96).…”

Section: Future Trendsmentioning

confidence: 99%

The Intriguing History of Cancer Immunotherapy

2019

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Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.

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Section: Future Trendsmentioning

confidence: 99%

The Intriguing History of Cancer Immunotherapy

2019

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“…This background has led to design directed-CRISPR/Cas9 technology in order to disrupt immune checkpoints. Some studies suggest an improvement in the anti-tumor efficacy and clinical outcome using these next generation modified CAR T-cells (157)(158)(159).…”

Section: Increasing Car T-cell Persistencementioning

confidence: 99%

Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma

2020

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Multiple myeloma (MM) remains an incurable disease regardless of recent advances in the field. Therefore, a substantial unmet need exists to treat patients with relapsed/refractory myeloma. The use of novel agents such as daratumumab, elotuzumab, carfilzomib, or pomalidomide, among others, usually cannot completely eradicate myeloma cells. Although these new drugs have had a significant impact on the prognosis of MM patients, the vast majority ultimately become refractory or can no longer be treated due to toxicity of prior treatment, and thus succumb to the disease. Cellular therapies represent a novel approach with a unique mechanism of action against myeloma with the potential to defeat drug resistance and achieve long-term remissions. Genetic modification of cells to express a novel receptor with tumor antigen specificity is currently being explored in myeloma. Chimeric antigen receptor gene-modified T-cells (CAR T-cells) have shown to be the most promising approach so far. CAR T-cells have shown to induce durable complete remissions in other advanced hematologic malignancies like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). With this background, significant efforts are underway to develop CAR-based therapies for MM. Currently, several antigen targets, including CD138, CD19, immunoglobulin kappa (Ig-Kappa) and B-cell maturation antigen (BCMA), are being used in clinical trials to treat myeloma patients. Some of these trials have shown promising results, especially in terms of response rates. However, the absence of a plateau is observed in most studies which correlates with the absence of durable remissions. Therefore, several potential limitations such as lack of effectiveness, off-tumor toxicities, and antigen loss or interference with soluble proteins could hamper the efficacy of CAR T-cells in myeloma. In this review, we will focus on clinical outcomes reported with CAR T-cells in myeloma, as well as on CAR T-cell limitations and how to overcome them with next generation of CAR T-cells.

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“…In order to limit such on‐target/off‐tumor toxicities, a series of strategies have already been described including, for example, the use of suicide genes, the CRISPR/Cas9 system, or targeting of co‐expressed surface antigens, eg, a non‐functional surface receptor molecule such as a truncated version of the epidermal growth factor receptor (EGFR) with Cetuximab . All of these technologies are designed to eliminate the CAR T cells in case they behave improperly.…”

Section: Achievements and Challengesmentioning

confidence: 99%

Theranostic CAR T cell targeting: A brief review

Arndt

Bachmann

Bergmann

et al. 2019

Labelled Comp Radiopharmac

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More than hundred years ago, Paul Ehrlich postulated that our immune system should be able to recognize tumor cells. Just recently, the development of check point inhibitors, bispecific antibodies, and T cells genetically modified to express chimeric antigen receptors (CARs) underlines the true power of our immune system. T cells genetically modified with CARs can lead to complete remission of malignant hematologic diseases. However, they can also cause life‐threatening side effects. In case of cytokine release syndrome, tumor lysis syndrome, or deadly side effects on the central nervous system, an emergency shut down of CAR T cells is needed. Targeting of tumor‐associated antigens that are also expressed on vital tissues require a possibility to repeatedly switch the activity of CAR T cells on and off on demand and to follow the treatment by imaging. Theranostic, modular CARs such as the UniCAR system may help to overcome these problems.

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CRISPR/Cas9 and CAR-T cell, collaboration of two revolutionary technologies in cancer immunotherapy, an instruction for successful cancer treatment

Cited by 80 publications

References 50 publications

The Intriguing History of Cancer Immunotherapy

The Intriguing History of Cancer Immunotherapy

Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma

Theranostic CAR T cell targeting: A brief review

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