CAR-expressing NK cells for cancer therapy: a new hope

Xia, Jufeng; Minamino, Shuichi; Kuwabara, Kazuma

doi:10.5582/bst.2020.03308

Cited by 28 publications

(20 citation statements)

References 57 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In both studies, the retroviral vector ectopically produced IL15 that is crucial for NK cell survival and conditionally expressed a caspase 9 (iC9)- an inducible suicide gene that could be activated to shut off the system by eliminating transduced cells when needed. Though retroviral vector systems have high transfection efficiency, the cDNA can integrate into the NK cell genome causing insertional mutagenesis and sometimes an induction of immune response ( 112 ).…”

Section: Delivery Systems To Engineer Nk Cellsmentioning

confidence: 99%

Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

et al. 2021

View full text Add to dashboard Cite

Natural killer cells (NK cells) are the first line of the innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected and malignant cells through a balancing play of inhibitory and stimulatory receptors. In pre-clinical investigational studies, NK cells show promising anti-tumor effects and are used in adoptive transfer of activated and expanded cells, ex-vivo. NK cells express co-stimulatory molecules that are attractive targets for the immunotherapy of cancers. Recent clinical trials are investigating the use of CAR-NK for different cancers to determine the efficiency. Herein, we review NK cell therapy approaches (NK cell preparation from tissue sources, ways of expansion ex-vivo for “off-the-shelf” allogeneic cell-doses for therapies, and how different vector delivery systems are used to engineer NK cells with CARs) for cancer immunotherapy.

show abstract

Section: Delivery Systems To Engineer Nk Cellsmentioning

confidence: 99%

Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

et al. 2021

View full text Add to dashboard Cite

show abstract

“… 149 CAR-NK cell consists of isolating NK cells and modify these cells to express CAR that targets a tumor-specific protein for instance and then re-infuse them back into the recipient. 150 , 151 CAR-modified human pluripotent stem cells might hold the capacity to produce functional CAR NK cells continuously, a potential solution to deal with the relative shorter life span of NK cells. 152 Although NK92 cell line is often considered for application in NK cell therapy based clinical trials, they have to be irradiated due to the reason they are aneuploid.…”

Section: Methodsmentioning

confidence: 99%

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

Zeng

2022

DDDT

View full text Add to dashboard Cite

The COVID-19 has plunged the world into a pandemic that affected millions. The continually emerging new variants of concern raise the question as to whether the existing vaccines will continue to provide sufficient protection for individuals from SARS-CoV-2 during natural infection. This narrative review aims to briefly outline various immunotherapeutic options and discuss the potential of clustered regularly interspaced short palindromic repeat (CRISPR Cas system technology against COVID-19 treatment as specific cure. As the development of vaccine, convalescent plasma, neutralizing antibodies are based on the understanding of human immune responses against SARS-CoV-2, boosting human body immune responses in case of SARS-CoV-2 infection, immunotherapeutics seem feasible as specific cure against COVID-19 if the present challenges are overcome. In cell based therapeutics, apart from the high costs, risks and side effects, there are technical problems such as the production of sufficient potent immune cells and antibodies under limited time to treat the COVID-19 patients in mild conditions prior to progression into a more severe case. The CRISPR Cas technology could be utilized to refine the specificity and safety of CAR-T cells, CAR-NK cells and neutralizing antibodies against SARS-CoV-2 during various stages of the COVID-19 disease progression in infected individuals. Moreover, CRISPR Cas technology are proposed in hypotheses to degrade the viral RNA in order to terminate the infection caused by SARS-CoV-2. Thus personalized cocktails of immunotherapeutics and CRISPR Cas systems against COVID-19 as a strategy might prevent further disease progression and circumvent immunity escape.

show abstract

“…Besides, PB-NK cells express a wide range of active receptors and thus hold potential as splendid sources for adoptive CAR-NK cell generation (Fig. 1 ) [ 21 , 35 ]. In general, resting PB-NK cells reveal a tremendous proliferative CD3 − CD56 bright cellular phenotype and are capable of secreting immunomodulatory cytokines, while the CD3 − CD56 dim counterpart possesses highly cytotoxicity and poor proliferation in response to cytokine stimulation (e.g., IL-2) [ 36 ].…”

Section: Cell Sources For Car-nk Cellsmentioning

confidence: 99%

“…2 , Table 1 ) [ 55 ]. The intracellular activating signaling domains (e.g., CD137, CD28) mainly mediate the activation and cytotoxicity of CAR-NK cells, while the extracellular antigen binding domains (e.g., the single-chain variable fragments) recognize the specific antigen of tumor cells [ 21 ]. For example, Quintarelli and the colleagues reported the successful design of retroviral plasmid carrying the cassettes of a second-generation CD19-CAR construct and transduced into PB-NK cells for Bcp-ALL management [ 40 ].…”

Section: Construction Of Carsmentioning

confidence: 99%

“…In consequence, state-of-the-art renewal has turned to rediscover the immune recognition and eradication of tumor cells by comminating with immune checkpoint blockade (e.g., CTLA4, PD-1/PD-L1), and in particular, to harness the innate immune response with moderate cytotoxicity and reduced adverse effects [ 17 , 18 ]. Of the indicated innate immune cells such as macrophages (Mø) and dendritic cells (DCs), autologous or allogeneic NK cells are adequate to fulfill the biofunction of combating malignant tumors and pathogenic microorganisms via paracrine effects (e.g., IFN-γ, GM-CSF), antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cytolytic effect dispense with preliminary antigen presentation as well as manipulating other immune contextures to recognize and attack cancer cells [ 1 , 5 , 19 – 21 ]. However, the heterogeneous tumor cells with genetic or epigenetic variations are also sufficient to elude the immunological surveillance and even reversely suppress NK cell cytotoxicity by interdicting the corresponding activating receptors [ 5 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CAR-NK cells for cancer immunotherapy: from bench to bedside

et al. 2022

View full text Add to dashboard Cite

Natural killer (NK) cells are unique innate immune cells and manifest rapid and potent cytotoxicity for cancer immunotherapy and pathogen removal without the requirement of prior sensitization or recognition of peptide antigens. Distinguish from the T lymphocyte-based cythotherapy with toxic side effects, chimeric antigen receptor-transduced NK (CAR-NK) cells are adequate to simultaneously improve efficacy and control adverse effects including acute cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GVHD). Moreover, considering the inherent properties of NK cells, the CAR-NK cells are “off-the-shelf” product satisfying the clinical demand for large-scale manufacture for cancer immunotherapy attribute to the cytotoxic effect via both NK cell receptor-dependent and CAR-dependent signaling cascades. In this review, we mainly focus on the latest updates of CAR-NK cell-based tactics, together with the opportunities and challenges for cancer immunotherapies, which represent the paradigm for boosting the immune system to enhance antitumor responses and ultimately eliminate malignancies. Collectively, we summarize and highlight the auspicious improvement in CAR-NK cells and will benefit the large-scale preclinical and clinical investigations in adoptive immunotherapy.

show abstract

CAR-expressing NK cells for cancer therapy: a new hope

Cited by 28 publications

References 57 publications

Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

CAR-NK cells for cancer immunotherapy: from bench to bedside

Contact Info

Product

Resources

About