Advances and challenges in chimeric antigen receptor‐natural killer cell immunotherapy for cancer DOI Open Access
Hind Rafei, Katayoun Rezvani

British Journal of Haematology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Chimeric antigen receptor (CAR)‐natural killer (NK)‐cell therapy has emerged as a promising strategy in the treatment of haematological malignancies and solid cancers. Leveraging innate immune properties NK cells, CAR‐NK‐cell therapies offer potential advantages for cell therapy, including safety use allogeneic setting reduced risk toxicity. This Nutshell provides an overview latest advancements challenges that remain.

Language: Английский

CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors DOI Creative Commons
Lei Peng, Giacomo Sferruzza,

Luojia Yang

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

Citations

31
Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy DOI Open Access
Joo Dong Park, Ha Eun Shin,

Y. An

et al.

Annals of Laboratory Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Joo Dong Park, M.S., Ha Eun Shin, Ph.D., Yeon Su An, B.S., Hye Jung Jang, Juwon Se-Na Kim, Chun Gwon and Wooram Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2024.0380

Citations

2
In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy DOI
Lei Peng, Paul Renauer, Giacomo Sferruzza

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Language: Английский

Citations

11
Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies DOI Creative Commons

Yi Du,

Yang Yang, Bohao Zheng

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle haystack at level. In cancer research, gene mutations are closely related tumor development, metastasis, and recurrence, use of state-of-the-art powerful technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), search for most critical genes or coding products provides us with new possibility further refine mapping provide possibilities treatment patients. The CRISPR refined atlas provided Immunotherapy, highly promising method, validated clinic, but could only meet needs small proportion Finding immunotherapy targets is key future immunotherapy. Here, we revisit application immunology from different perspectives, selection diverse vitro vivo models potential immune checkpoints potentiating CAR-T cells. data will offer fresh therapeutic clues

Language: Английский

Citations

1
Chimeric Cytokine Receptor TGF-β RⅡ/IL-21R Improves CAR-NK Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Gastric Cancer DOI Creative Commons

Yaojun Ren,

Min Xue,

Xinhui Hui

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107637 - 107637

Published: Jan. 29, 2025

Gastric cancer remains a significant global health burden, characterized by regional variations in incidence and poor survival prospects advanced stages. Natural killer (NK) cells play crucial role the body's anti-cancer defense, chimeric antigen receptor (CAR)-NK cell therapy is gaining attention as cutting-edge promising treatment method. This study aims to tackle challenge of TGF-β-mediated tumor immune evasion within immunosuppressive microenvironment designing novel cytokine TRII/21R, which consists extracellular domains TGF-β II (TRII) transmembrane intracellular IL-21 (21R) can convert signal from (TME) into an NK activation through IL-21R-STAT3 pathway. We successfully constructed NKG2D-CAR-NK expressing TRII/21R demonstrated strong anti-tumor activity against both vitro vivo. The co-expression CAR-NK enhanced cytotoxicity, promoted proliferation capabilities, reduced expression exhaustion markers. In xenograft mouse model, TRII/21R-CAR-NK significantly inhibited growth improved rate tumor-bearing mice compared receiving control cells. Additionally, cells' infiltration, activation, persistence tumor, indicating robust response mediated JAK-STAT3 signaling underscores therapeutic potential TRII/21R-modified breakthrough strategy for combating cancer.

Language: Английский

Citations

1
Engineering innate immune cells for cancer immunotherapy DOI
Mubin Tarannum,

Xizhong Ding,

Marta Barisa

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: 43(4), P. 516 - 533

Published: April 1, 2025

Language: Английский

Citations

1
Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability DOI
Dong-sheng Bai,

Zhenkun Cao,

Nivedita Attada

et al.

Nature Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

Citations

0
Transcriptional signature of rapidly responding NK cells reveals S1P5 and CXCR4 as anti-tumor response disruptors DOI Creative Commons

Marta Puig-Gámez,

Martijn Van Attekum,

Torsten Theis

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 28, 2025

Natural killer (NK) cells are prototypic cytotoxic innate lymphocytes that can kill target cells, such as tumor in the absence of antigen-restriction. Peripheral NK exhibit a high degree heterogeneity. Here, we set out to broadly assess intrinsic modulators cell degranulation an unbiased manner. We stimulated human primary blood-borne pre-treated with different cytokine regimens HCT116 colon cancer line and used detection lysosome-associated membrane glycoprotein 1 (LAMP1) identifier rapid degranulation. RNA sequencing FACS-sorted LAMP1hi showed CXCR4 S1PR5 were top down-regulated genes. Using compounds modulate activity S1P receptor family members S1P1 S1P5, confirmed they play important immunosuppressive role cytotoxicity. Mechanistically, engagement S1P1/5 receptors triggered phosphorylation p42 Ca2+ influx. activation promoted S1P5 upregulation vice versa, joint both amplified defect Intriguingly, samples expression synthesis their ligands themselves appear be coordinately regulated. Together, these data suggest specifically simultaneously targeting microenvironment (TME) could beneficial strategy unleash full potential effector tumor.

Language: Английский

Citations

0
Unraveling the future of genomics: CRISPR, single-cell omics, and the applications in cancer and immunology DOI Creative Commons
A Vipin Menon, Bicna Song, Lumen Chao

et al.

Frontiers in Genome Editing, Journal Year: 2025, Volume and Issue: 7

Published: April 11, 2025

The CRISPR system has transformed many research areas, including cancer and immunology, by providing a simple yet effective genome editing system. Its simplicity facilitated large-scale experiments to assess gene functionality across diverse biological contexts, generating extensive datasets that boosted the development of computational methods machine learning/artificial intelligence applications. Integrating with single-cell technologies further advanced our understanding function its role in processes, unprecedented insights into human biology disease mechanisms. This powerful combination accelerated AI-driven analyses, enhancing diagnostics, risk prediction, therapeutic innovations. review provides comprehensive overview CRISPR-based systems, highlighting their advancements, current progress, challenges, future opportunities, especially immunology.

Language: Английский

Citations

0
Chimeric antigen receptor NK cells for breast cancer immunotherapy DOI

Nisha Wu,

Ning Yang, Shiqi Zhang

et al.

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102943 - 102943

Published: April 1, 2025

Language: Английский

Citations

0