Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

Kim, Nayoung; Lee, Dong-Hee; Choi, Woo Seon; Yi, Eunbi; Kim, Hyo-Jeong; Kim, Jung Min; Jin, Hyung‐seung; Kim, Hun Sik

doi:10.5483/bmbrep.2021.54.1.214

Cited by 9 publications

(4 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, NK cell alloreactivity can eliminate leukemia relapse effectively ( 5 , 6 ). The safety and efficacy of NK cell therapy have been evaluated in various tumors since ( 7 ). Furthermore, recent progress in immune cell therapy with the chimeric antigen receptor (CAR) provides novel therapeutic possibilities for NK cells.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

Kim,

Yi,

Lee

et al. 2024

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells in vivo without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.

show abstract

Section: Introductionmentioning

confidence: 99%

Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

Kim,

Yi,

Lee

et al. 2024

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, using single-cell RNA sequencing (scRNAseq) approach, elevated CEACAM1 expression was identified both in blood and bronchoalveolar samples of COVID-19 patients and correlated with enhanced viral load [25]. Increased CEACAM1 expression was also demonstrated to play a role in immune evasion, cancer progression and immune checkpoint modulation [26][27][28]. Based on the involvement of CE-ACAM1 in T cell exhaustion, CEACAM1 has taken a considerable attention as a plausible target in immunotherapy in cancer [29].…”

Section: Introductionmentioning

confidence: 99%

Integrative profiling of CEACAM1 in different malignancies with implications on the SARS-CoV-2 infection genes ACE2 and TMPRSS2

Acar

2023

Hacettepe Journal of Biology and Chemistry

View full text Add to dashboard Cite

Increasing number of evidence demonstrated increased SARS-CoV-2 infection risk in cancer. Despite various studies shed light on SARS-CoV-2 mediated pathways upregulated in cancer, there is still ongoing efforts to reveal underlying mechanisms of elevated risk for COVID-19 disease in cancer. Given critical role of CEACAM1 in immune exhaustion and immune deregulation observed both in cancer and COVID-19, systematic characterization of CEACAM1 in different malignancies was performed with an ultimate aim to identify the involvement of CEACAM1 in enhanced COVID-19 susceptibility in cancer patients. Here we show that CEACAM1 expression was upregulated in a number of TCGA samples. In addition, CEACAM1 expression was positively correlated with SARS-CoV-2 infection genes in TCGA samples. Single-cell RNA sequencing analysis results of COVID-19 positive patients indicated upregulation of CEACAM1 expression. Furthermore, CEACAM1 expression was associated with HAVCR2, an immune checkpoint marker, and there was a correlation between CEACAM1 and HAVCR2 levels in different TCGA samples. Collectively, CEACAM1 might provide increased susceptibility of COVID-19 disease in cancer patients which might be explained with its interaction with HAVCR2.

show abstract

“…To overcome the limitations of CAR-T cell therapy, natural killer (NK) cells are suitable candidates for cancer immunotherapy. They are not major histocompatibility complex (MHC)-restricted and are thus less likely to elicit GVHD while retaining anti-tumor activity via degranulation of cytolytic molecules, including granzyme and perforin, and cytokine secretion (11). In addition, NK cells have short lifespans, which may prevent cytokine release syndrome.…”

Section: Introductionmentioning

confidence: 99%

CD19/CD22 bispecific chimeric antigen receptor‑NK‑92 cells are developed and evaluated

et al. 2023

View full text Add to dashboard Cite

Anti-CD19 chimeric antigen receptor (CAR)-T cells have improved the outcomes of patients with B cell leukemia and lymphoma. However, their applications and positive outcomes remain limited. CAR-T cells are currently restricted to autologous blood as their source and their use can lead to downregulation of CD19 expression along with complications such as graft-versus-host disease and cytokine release syndrome. The present study aimed to develop anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyze them in natural killer (NK)-92 cells, a human NK cell line, in vitro and in vivo. Anti-CD19/CD22 CAR-NK-92 cell cytotoxicity was assessed by the survival of target cells and counted using flow cytometry. Anti-CD22/CD19 and loop-structured anti-CD19/CD22 bi-specific CAR-NK-92 cells showed improved efficacy against OCI-Ly7 cells, a human B cell lymphoma cell line, compared with other CAR structures. These results demonstrate the potential of anti-CD19/CD22 bispecific CAR-NK cells and suggested that optimizing CAR structures in NK cells can improve the efficacy of CAR therapy.

show abstract

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

Cited by 9 publications

References 141 publications

Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

Integrative profiling of CEACAM1 in different malignancies with implications on the SARS-CoV-2 infection genes ACE2 and TMPRSS2

CD19/CD22 bispecific chimeric antigen receptor‑NK‑92 cells are developed and evaluated

Contact Info

Product

Resources

About