Directly reprogrammed natural killer cells for cancer immunotherapy

Kim, Han-Seop; Kim, Jae Yun; Seol, Binna; Song, Cho Lok; Jeong, Ji Eun; Cho, Yee Sook

doi:10.1038/s41551-021-00768-z

Cited by 19 publications

(14 citation statements)

References 49 publications

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“…The constructed NK cells could specifically recognize EGFR-overexpressing tumor cells and cause efficient tumor cell lysis, thus presenting an enhanced immunotherapeutic efficacy both in vitro and in vivo . Recently, Kim et al reported an easy and rapid route to directly reprogram human somatic cells into CD56 + CD16 + NK cells (drNKs) using pluripotency transcription factors and an optimized reprogramming medium, which were perfectly capable of killing multiple tumors and presented a strong innate-adaptive immunomodulatory activity (Figure b) …”

Section: Immune Cell-based Drug Carriers For Cancer Immunotherapymentioning

confidence: 99%

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

et al. 2023

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Immunotherapy continues to be in the spotlight of oncology therapy research in the past few years and has been proven to be a promising option to modulate one's innate and adaptive immune systems for cancer treatment. However, the poor delivery efficiency of immune agents, potential off-target toxicity, and nonimmunogenic tumors significantly limit its effectiveness and extensive application. Recently, emerging biomaterial-based drug carriers, including but not limited to immune cells and bacteria, are expected to be potential candidates to break the dilemma of immunotherapy, with their excellent natures of intrinsic tumor tropism and immunomodulatory activity. More than that, the tiny vesicles and physiological components derived from them have similar functions with their source cells due to the inheritance of various surface signal molecules and proteins. Herein, we presented representative examples about the latest advances of biomaterial-based delivery systems employed in cancer immunotherapy, including immune cells, bacteria, and their derivatives. Simultaneously, opportunities and challenges of immune cells and bacteria-based carriers are discussed to provide reference for their future application in cancer immunotherapy.

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Section: Immune Cell-based Drug Carriers For Cancer Immunotherapymentioning

confidence: 99%

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

et al. 2023

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“…NK cells derived from cord blood (CB-NK) are less mature before and after expansion, easier to engineer and easily accessible as well (108). Additionally, NK cells can be differentiated from hematopoietic stem cells (HSCs) (109,110), induced pluripotent stem cells (iPSCs) (75) as well as from other immune cells using direct reprogramming (drNK) within a few days (111). These cells are more difficult to manufacture in research facilities due to the added complexity of differentiating NK cells in a first step, however, stem cells pose a virtually unlimited source of homogenous, highly active NK cell populations.…”

Section: Challenges In Nk Cell Based Therapiesmentioning

confidence: 99%

“…These cells are more difficult to manufacture in research facilities due to the added complexity of differentiating NK cells in a first step, however, stem cells pose a virtually unlimited source of homogenous, highly active NK cell populations. However, if signaling and immune-suppressive factors of the TME affect NK cells of all sources in the same manner is still an open question, as most studies utilize just a single source of cells, with few exceptions (111), and side-by-side comparisons, especially under challenging conditions, are scarce. Possibly, genetic engineering has to be adjusted both to source and the anticipated tumor environment that needs to be overcome, therefore, differential CAR signaling, metabolic reprogramming or deletion of different inhibitory receptors need to be functionally assessed and predictive markers for NK cell in vivo efficacy established.…”

Section: Challenges In Nk Cell Based Therapiesmentioning

confidence: 99%

Taking Lessons from CAR-T Cells and Going Beyond: Tailoring Design and Signaling for CAR-NK Cells in Cancer Therapy

et al. 2022

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Cancer immunotherapies utilize the capabilities of the immune system to efficiently target malignant cells. In recent years, chimeric antigen receptor (CAR) equipped T cells showed promising results against B cell lymphomas. Autologous CAR-T cells require patient-specific manufacturing and thus extensive production facilities, resulting in high priced therapies. Along with potentially severe side effects, these are the major drawbacks of CAR-T cells therapies. Natural Killer (NK) cells pose an alternative for CAR equipped immune cells. Since NK cells can be safely transferred from healthy donors to cancer patients, they present a suitable platform for an allogeneic “off-the-shelf” immunotherapy. However, administration of activated NK cells in cancer therapy has until now shown poor anti-cancer responses, especially in solid tumors. Genetic modifications such as CARs promise to enhance recognition of tumor cells, thereby increasing anti-tumor effects and improving clinical efficacy. Although the cell biology of T and NK cells deviates in many aspects, the development of CAR-NK cells frequently follows within the footsteps of CAR-T cells, meaning that T cell technologies are simply adopted to NK cells. In this review, we underline the unique properties of NK cells and their potential in CAR therapies. First, we summarize the characteristics of NK cell biology with a focus on signaling, a fine-tuned interaction of activating and inhibitory receptors. We then discuss why tailored NK cell-specific CAR designs promise superior efficacy compared to designs developed for T cells. We summarize current findings and developments in the CAR-NK landscape: different CAR formats and modifications to optimize signaling, to target a broader pool of antigens or to increase in vivo persistence. Finally, we address challenges beyond NK cell engineering, including expansion and manufacturing, that need to be addressed to pave the way for CAR-NK therapies from the bench to the clinics.

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“…Early methods employed stromal cell lines in both of these steps (Ni et al 2011 ). Alternatively, somatic cells have recently been reprogrammed using pluripotency transcription factors to generate NK cells (Kim et al 2021 ). More recently, systems to expand iPSC-NK cells without feeder cells (Knorr et al 2013 ; Matsubara et al 2019 ; Ueda et al 2020 ) and obviating the need for embryoid body formation and CD34 + cell purification (Zeng et al 2017 ) have been reported.…”

Section: Ipsc-derived Nk Cells and Engineered Derivativesmentioning

confidence: 99%

Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

Mazza

Maher

2021

Arch. Immunol. Ther. Exp.

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Technologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.

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Directly reprogrammed natural killer cells for cancer immunotherapy

Cited by 19 publications

References 49 publications

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

Taking Lessons from CAR-T Cells and Going Beyond: Tailoring Design and Signaling for CAR-NK Cells in Cancer Therapy

Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

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