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嵌合抗原受体自然杀伤(CAR-NK)细胞疗法治疗转移性黑色素瘤:潜力与展望。

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects.

机构信息

Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Cells. 2023 Nov 30;12(23):2750. doi: 10.3390/cells12232750.


DOI:10.3390/cells12232750
PMID:38067178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10706172/
Abstract

Melanoma is among the most lethal forms of cancer, accounting for 80% of deaths despite comprising just 5% of skin cancer cases. Treatment options remain limited due to the genetic and epigenetic mechanisms associated with melanoma heterogeneity that underlie the rapid development of secondary drug resistance. For this reason, the development of novel treatments remains paramount to the improvement of patient outcomes. Although the advent of chimeric antigen receptor-expressing T (CAR-T) cell immunotherapies has led to many clinical successes for hematological malignancies, these treatments are limited in their utility by their immune-induced side effects and a high risk of systemic toxicities. CAR natural killer (CAR-NK) cell immunotherapies are a particularly promising alternative to CAR-T cell immunotherapies, as they offer a more favorable safety profile and have the capacity for fine-tuned cytotoxic activity. In this review, the discussion of the prospects and potential of CAR-NK cell immunotherapies touches upon the clinical contexts of melanoma, the immunobiology of NK cells, the immunosuppressive barriers preventing endogenous immune cells from eliminating tumors, and the structure and design of chimeric antigen receptors, then finishes with a series of proposed design innovations that could improve the efficacy CAR-NK cell immunotherapies in future studies.

摘要

黑色素瘤是最致命的癌症之一,尽管仅占皮肤癌病例的 5%,但其死亡率却占 80%。由于与黑色素瘤异质性相关的遗传和表观遗传机制导致继发性药物耐药性迅速发展,治疗选择仍然有限。出于这个原因,开发新的治疗方法对于改善患者的预后仍然至关重要。尽管嵌合抗原受体表达 T(CAR-T)细胞免疫疗法的出现为血液恶性肿瘤带来了许多临床成功,但这些治疗方法受到免疫诱导的副作用和高全身性毒性的限制,其应用受到限制。CAR 自然杀伤(CAR-NK)细胞免疫疗法是 CAR-T 细胞免疫疗法的一种特别有前途的替代方法,因为它们具有更有利的安全性特征,并具有微调细胞毒性活性的能力。在这篇综述中,CAR-NK 细胞免疫疗法的前景和潜力的讨论涉及黑色素瘤的临床背景、NK 细胞的免疫生物学、阻止内源性免疫细胞消除肿瘤的免疫抑制障碍,以及嵌合抗原受体的结构和设计,最后提出了一系列可能的设计创新,以提高 CAR-NK 细胞免疫疗法在未来研究中的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/57078b0d1322/cells-12-02750-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/f46efe0d377c/cells-12-02750-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/a54a464d6e31/cells-12-02750-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/8fff9e6da167/cells-12-02750-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/57078b0d1322/cells-12-02750-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/f46efe0d377c/cells-12-02750-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/a54a464d6e31/cells-12-02750-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/8fff9e6da167/cells-12-02750-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edde/10706172/57078b0d1322/cells-12-02750-g004.jpg

相似文献

[1]
CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects.

Cells. 2023-11-30

[2]
Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.

BMC Cancer. 2022-11-25

[3]
Engineering CAR-NK cells to secrete IL-15 sustains their anti-AML functionality but is associated with systemic toxicities.

J Immunother Cancer. 2021-12

[4]
Advances in CAR-NK cell therapy for hematological malignancies.

Front Immunol. 2024

[5]
Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity.

Br J Haematol. 2021-4

[6]
Preclinical Assessment of Suitable Natural Killer Cell Sources for Chimeric Antigen Receptor Natural Killer-Based "Off-the-Shelf" Acute Myeloid Leukemia Immunotherapies.

Hum Gene Ther. 2019-3-18

[7]
In Vitro Evaluation of CD276-CAR NK-92 Functionality, Migration and Invasion Potential in the Presence of Immune Inhibitory Factors of the Tumor Microenvironment.

Cells. 2021-4-26

[8]
Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer.

Cells. 2020-6-2

[9]
CAR-NK Cells: From Natural Basis to Design for Kill.

Front Immunol. 2021

[10]
Preclinical and clinical studies of CAR-NK-cell therapies for malignancies.

Front Immunol. 2022

引用本文的文献

[1]
Pigmented skin lesions with atypical histopathology indicating a diagnosis of multiple metastases of melanoma: A case report.

Oncol Lett. 2025-5-27

[2]
Development of Personalized Strategies for Precisely Battling Malignant Melanoma.

Int J Mol Sci. 2024-5-4

本文引用的文献

[1]
Efficacy and Safety of Rechallenge with BRAF/MEK Inhibitors in Advanced Melanoma Patients: A Systematic Review and Meta-Analysis.

Cancers (Basel). 2023-7-25

[2]
GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer.

J Hematol Oncol. 2023-7-20

[3]
Off-the-shelf CAR-engineered natural killer cells targeting FLT3 enhance killing of acute myeloid leukemia.

Blood Adv. 2023-10-24

[4]
Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma.

Cancer Res Commun. 2023-5

[5]
The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy.

Cancers (Basel). 2023-4-16

[6]
B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer.

Cell Death Discov. 2023-5-6

[7]
EBV-Upregulated B7-H3 Inhibits NK cell-Mediated Antitumor Function and Contributes to Nasopharyngeal Carcinoma Progression.

Cancer Immunol Res. 2023-6-2

[8]
Axl contributes to efficient migration and invasion of melanoma cells.

PLoS One. 2023

[9]
Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance.

Cancer Cell. 2023-2-13

[10]
Engineering c-Met-CAR NK-92 cells as a promising therapeutic candidate for lung adenocarcinoma.

Pharmacol Res. 2023-2

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