iPSC-Derived Natural Killer Cells for Cancer Immunotherapy

Karagiannis, Peter; Kim, Shin Il

doi:10.14348/molcells.2021.0078

Cited by 46 publications

(35 citation statements)

References 53 publications

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“…It was frequently objected that NK cells are never antigen-specific, an argument that is no longer valid with the arrival of CAR-NK cells in preclinical studies and clinical trials. Adult iPSC allow to obtain high numbers of NK cells, are easily accessible (theoretically, any somatic cell type might be reprogrammable into iPSC) because mostly skin fibroblasts or PBMC are used [ 74 , 75 ], and avoid the ethically highly debatable approach with embryonic stem cells. Once suitable homogeneous iPSC clones are selected, they can be banked and are further expandable and differentiable into the desired end product.…”

Section: Adoptive Transfer Of Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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Section: Adoptive Transfer Of Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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“…In the case of hiPSCs, they retain the genetic background of the donor [ 363 ]. Both hiPSCs and hESCs have allowed the study of human cells which are not normally accessible to study in the human body (for example, neurons and glial cells of the human CNS) and, therefore, have boosted the possibilities in medical research employing human cell lines, permitting the study of mechanisms of human development [ 363 , 364 ]; in vitro disease modelling, including in cancer research [ 365 , 366 , 367 ]; in the development of assays and platforms for drug screening campaigns [ 355 , 368 , 369 ]; in patient stratification and in the development of cell replacement strategies [ 355 , 363 ]. The pioneer monolayer cultures gave way to organoids, spheroids, organ-on-a-chip approaches and more recently assembloids, which employ single cell types or a multitude of different cellular types [ 355 , 360 , 370 , 371 , 372 , 373 ].…”

Section: Current Challenges and Future Perspectives In Uveal Melanomamentioning

confidence: 99%

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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“…NK cells express activating receptors, such as NCRs, NKG2D, and DNAM-1, which may be engaged synergistically and independently from the CAR, triggering NK killing capability and potentially bypassing loss of targeted antigens as a tumor escape mechanism. NKs could also be derived from various sources such as blood, cord-blood, and differentiated in vitro from induced pluripotent stem cells (iPSC) [ 69 ]. The immortalized NK92 cell line was shown to be well tolerated in clinical trials.…”

Section: Off-the-shelf Carsmentioning

confidence: 99%

From Hematopoietic Stem Cell Transplantation to Chimeric Antigen Receptor Therapy: Advances, Limitations and Future Perspectives

Voynova

Kovalovsky

2021

Cells

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Chimeric antigen receptor (CAR) T-cell therapy was envisioned as a mechanism to re-direct effector T-cells to eliminate tumor cells. CARs are composed of the variable region of an antibody that binds a native cancer antigen coupled to the signaling domain of a TCR and co-stimulatory molecules. Its success and approval by the U.S. Food and Drug Administration for the treatment of B-cell malignancies revolutionized the immunotherapy field, leading to extensive research on its possible application for other cancer types. In this review, we will focus on the evolution of CAR-T cell therapy outlining current technologies as well as major obstacles for its wide application. We will highlight achievements, the efforts to increase efficacy and to evolve into an off-the-shelf treatment, and as a possible future treatment for non-cancer related diseases.

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iPSC-Derived Natural Killer Cells for Cancer Immunotherapy

Cited by 46 publications

References 53 publications

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

From Hematopoietic Stem Cell Transplantation to Chimeric Antigen Receptor Therapy: Advances, Limitations and Future Perspectives

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