Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer

Cao, Bihui; Liu, Manting; Wang, Lu; Liang, Biao; Feng, Yangbo; Chen, Xiaopei; Shi, Yuanyuan; Zhang, Jinling; Ye, Xiaodie; Tian, Yu; Zhi, Cheng; Li, Junping; Lian, Hui; Wu, Qingde; Zhang, Zhenfeng

doi:10.1016/j.bbrc.2020.01.053

Cited by 61 publications

(47 citation statements)

References 20 publications

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“…Additional targets being evaluated in recent clinical trials include a prostate-specific membrane antigen (PSMA) expressed over 100 times higher in prostate tumor tissues than normal prostate and the tumor differentiation antigen mesothelin in ovarian cancer [117,118]. CAR NK cells and CAR NKT cells have been reported to target MUC1, a glycoprotein that creates a significant barrier preventing drugs from binding to their targets on cancer cells [119].…”

Section: Targets For Car Nk Cellsmentioning

confidence: 99%

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

et al. 2020

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Natural killer (NK) cells are a critical component of the innate immune system. Chimeric antigen receptors (CARs) re-direct NK cells toward tumor cells carrying corresponding antigens, creating major opportunities in the fight against cancer. CAR NK cells have the potential for use as universal CAR cells without the need for human leukocyte antigen matching or prior exposure to tumor-associated antigens. Exciting data from recent clinical trials have renewed interest in the field of cancer immunotherapy due to the potential of CAR NK cells in the production of “off-the-shelf” anti-cancer immunotherapeutic products. Here, we provide an up-to-date comprehensive overview of the recent advancements in key areas of CAR NK cell research and identify under-investigated research areas. We summarize improvements in CAR design and structure, advantages and disadvantages of using CAR NK cells as an alternative to CAR T cell therapy, and list sources to obtain NK cells. In addition, we provide a list of tumor-associated antigens targeted by CAR NK cells and detail challenges in expanding and transducing NK cells for CAR production. We additionally discuss barriers to effective treatment and suggest solutions to improve CAR NK cell function, proliferation, persistence, therapeutic effectiveness, and safety in solid and liquid tumors.

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Section: Targets For Car Nk Cellsmentioning

confidence: 99%

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

et al. 2020

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“…NK cells have been engineered to express a particular NK‐adapted anti‐mesothelin SS1 CAR 39 . A more recent study confirmed the therapeutic effect of these CAR NK cells in OC 40 . This original approach will be used in an upcoming clinical trial involving OC patients (NCT03692637).…”

Section: The Usual Suspectsmentioning

confidence: 99%

SJI 2020 special issue: A catalogue of Ovarian Cancer targets for CAR therapy

et al. 2020

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Cell-based cancer immunotherapy represents a promising option for patients lacking treatment alternatives. It comprises the use of the immune system to destroy the tumour, ideally establishing an immunological memory response against the tumour. A very efficient method of attacking the tumour is to use effector cells, such as NK or T cells, either preselected in the tumour (tumour infiltrating lymphocytes, TILs) or with enhanced functions, such as tumour targeting through genetic manipulation. 1-6 In the latter, targeting of cells is achieved by overexpression of an antigen receptor, either a natural T cell Receptor (TCR), or an artificial Chimeric Antigen Receptor (CAR). These receptors will guide the effector cell to its target and trigger cytotoxic activity of the lymphocytes. This approach has proven very successful in liquid tumours; however, advanced solid tumours are more challenging to treat. It is becoming obvious that the two main pitfalls in solid tumour CAR development are the identification of cancer-restricted targets and the negative influence of the tumour microenvironment (TME). Ovarian cancer (OC) is one of the most lethal gynaecologic malignancies. Most OCs are epithelial ovarian carcinomas, with the most common of these being the serous type, which includes low and high-grade tumours. Women are usually diagnosed only at the advanced stage of the disease. Standard treatment comprise debulking surgery with the aim to remove all macroscopic tumour, preferably upfront, or after neoadjuvant chemotherapy. Surgery is followed by adjuvant chemotherapy and maintenance treatment in selected cases. However, even with a good initial response, the

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“…On the other hand, studies presented that Her2-CAR-T cells were able to suppress the growth potential of the human ovarian SKOV3 cell line expressing Her-2/ neu [56], and the use of the Meso-CAR-T cells [57] led to the inhibition of proliferation and promoted mice viability. Furthermore, 5T4-specific CAR T cells [106] and FRα-specific CAR T cells [58] [59].…”

Section: Ovarian Cancermentioning

confidence: 99%

“…Colorectal NKG2D [54], EP-CAM [55], HER2 [56], GUCY2C [57], TAG-72 [58], CD46 [58] Liver CEA [59], Glypican3 [60], AFP [61] Gastric Mesothelin [62], ANTXR1 [63], MUC3A [63], Trop2 [64], Claudin18.2 [66], NKG2D [28], HER2 [65,66], FR-α [67] Pancreatic MUC1 [68], Mesothelin [69], αvβ6 [70], CEA [71], PSCA [71], FAP [71], CD47 [72], HER2 [73], NKG2D [74] Renal CAIX [75] Melanoma GD2 [76], GSPG4 [77], Glypican3 [78], HER2 [79] Cervix αvβ6 [80], L1-CAM [81] Neuroblastoma GD2 [82,83], CD56 [84], Glypican 2 [85], CD171 [86] Glioblastoma EGFRvIII [87], HER2 [88], B7-H3 [89], NKG2D [90], CAIX [91], αvβ3, IL13Rα2 [92] Ovarian Mesothelin [62,93], αvβ6…”

Section: Cancer Antigenmentioning

confidence: 99%

CAR T cells in solid tumors: challenges and opportunities

et al. 2021

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Background CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

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Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer

Cited by 61 publications

References 20 publications

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

SJI 2020 special issue: A catalogue of Ovarian Cancer targets for CAR therapy

CAR T cells in solid tumors: challenges and opportunities

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