Phase I Clinical Trial Using Autologous Ex Vivo Expanded NK Cells and Cytotoxic T Lymphocytes for Cancer Treatment in Vietnam

Liêm, Nguyễn Thanh; Phong, Nguyen Van; Kien, Nguyen Trung; Anh, Bui Viet; Huyen, Truong Linh; Thao, Chu Thi Bich; Tu, Nguyen Dac; Hiep, Doan Trung; Thu, Do Thi Hoai; Nhung, Hoang Thi My

doi:10.3390/ijms20133166

Cited by 18 publications

(15 citation statements)

References 36 publications

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“…Survival and quality of life were increased in most patients. 26 Besides the number and the purity, another important entity in NK cellenrichment is to yield cytotoxic subset. Considering the conventional classification (based on the expression of CD16 and CD56), CD56 hi CD16 dim regulatory NK cells were observed to be decreased after expansion (25.321 vs. 7.39).…”

Section: Discussionmentioning

confidence: 99%

Autologous Natural Killer Cell-enrichment for Immune Cell Therapy: Preclinical Setting Phase, Shiraz Experience

Rezaeifard¹,

Heike²,

Masuyama³

et al. 2021

IJAAI

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Natural killer (NK) cell therapy has proven to be a promising approach for the treatment of malignancies. Osaki method for ex-vivo autologous NK cell expansion has been recently introduced in Japan. To start clinical trial phase I at Shiraz University of Medical Sciences in collaboration with the Japanese group, this preclinical setting study aimed to evaluate the proliferative efficacy of the method, the activation status of expanded autologous NK cells, and the likely unwanted contamination of the final cell product. Peripheral blood mononuclear cells (PBMCs) were isolated from 5 healthy individuals' peripheral blood and transferred directly to the specified initial culture bag containing anti-CD52 and anti-CD3 and Interleukin (IL)-2. The cells were cultured for 14-17 days in an incubator, during which the cells received condition media, and underwent several passages into bigger culture bags. All the procedures were carried out in a cleanroom and associated facilities. Before and after activation PBMCs were analyzed for their phenotype and cytotoxic activity; using flow cytometry and cytokine release assay. Our results indicated that NK (CD3-CD16+/-CD56+) cells were expanded 510-fold on average (range 200-1100 fold), and the purity of NK cells per whole lymphocytes exceeded 68%. The expanded cells were highly lytic as indicated by in-vitro cytotoxic assay, with a strong expression of Natural killer group 2 member D (NKG2D) and CD16. The prepared final cell products were negative for HCV, HBV, HIV, mycoplasma, and endotoxin. In the preclinical phase, large numbers of activated and un-contaminated NK cells from healthy individuals' peripheral blood were successfully generated. The method seems to provide ample clean cell product with no contamination and has the potential to be used for NK cell therapy in future clinical trials, suitable to be infused back to the donors in phase I clinical trial.

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Section: Discussionmentioning

confidence: 99%

Autologous Natural Killer Cell-enrichment for Immune Cell Therapy: Preclinical Setting Phase, Shiraz Experience

Rezaeifard¹,

Heike²,

Masuyama³

et al. 2021

IJAAI

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“…These cells, by their direct contact or in a TCR-dependent manner, attack the target cells and provide a safe harbor to other cells. Interestingly, CTLs could also destroy tumor cells through an MHC-independent manner attacking autologous tumor cells without affecting other cells within the area [96,97]. Cancer immunotherapy using transfer of TCR genes [98,99] or adoptive transfer of CTLs [100,101] has been facing an important problem in harvesting enough antigen-specific CTLs for therapy.…”

Section: Generation Of T Lymphocytes From Ipsc Technology: a New T-cementioning

confidence: 99%

Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

Nezhad

2021

Preprint

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CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR-Technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development and provides a roadmap for development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs. Keywords: CAR-T cell; iPSC; T cell; iPSC-derived T cell; tumor cell; therapeutic; off-the-shelf

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“…al. reported that this therapy (NK Cells and CTLs from Peripheral Blood) is not only safe and possible, but also could increase the quality of life for patients (Liem et al, 2019).…”

Section: Nk Cell Therapy Of Tumormentioning

confidence: 99%

“…al. reported that this therapy (NK Cells and CTLs from Peripheral Blood) is not only safe and possible, but also could increase the quality of life for patients(Liem et al, 2019). T A B L E 3 (Continued) , acute lymphoblastic lymphoma; AML, acute myeloid leukemia; CLL, chronic lymphocyte leukemia; CR, complete response; CRC, colorectal carcinoma; CY, cyclophosphamide; DSRCT, desmoplastic small round cell tumor; EWS, Ewing sarcoma; GVHD, graft versus host disease; MM, multiple myeloma; MRC, metastatic renal carcinoma; N/D, not determined; NSCLC, non-small cell lung carcinoma; PR, partial response; RCC, renal cell carcinoma; RMS, rhabdomyosarcoma; TBI, total body irradiation.…”

mentioning

confidence: 99%

Current progress in cancer immunotherapy based on natural killer cells

Bagheri

Barati

Aghebati‐Maleki

et al. 2020

Cell Biology International

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One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still is no definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the means of immunotherapy. As innate lymphocytes, NK cells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen‐specific. Latest insights into the biology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell‐dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T–cell‐targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy.

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Phase I Clinical Trial Using Autologous Ex Vivo Expanded NK Cells and Cytotoxic T Lymphocytes for Cancer Treatment in Vietnam

Cited by 18 publications

References 36 publications

Autologous Natural Killer Cell-enrichment for Immune Cell Therapy: Preclinical Setting Phase, Shiraz Experience

Autologous Natural Killer Cell-enrichment for Immune Cell Therapy: Preclinical Setting Phase, Shiraz Experience

Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

Current progress in cancer immunotherapy based on natural killer cells

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