Advances in natural killer cell therapies for breast cancer

Kiaei, Seyedeh Zahra Fotook; Nouralishahi, Alireza; Ghasemi-Rad, Mohammad; Barkhordar, Maryam; Ghaffari, Sasan; Kheradjoo, Hadis; Saleh, Mahshid; Mohammadzadehsaliani, Saman; Molaeipour, Zahra

doi:10.1111/imcb.12658

Cited by 8 publications

(2 citation statements)

References 179 publications

(441 reference statements)

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“…In order to avoid tumor-invading cytotoxic T lymphocytes detecting the presence of tumor cells, MHC-I expression on the surface of the tumor cell is often inhibited or eliminated. NK cell inhibitory receptors are able to detect this lack of MHC-I, and the immunogenic effect of NK cells is evident in their contribution to regulating the function of multiple immune cells, including DCs, macrophages, and T and B cells ( 15 ). Principal components of the TME are DCs, which are thought to be one of the most potent types of APC, and present antigens, including tumor-derived antigens, to T-cells.…”

Section: Tumor Immune Microenvironment and Breast Cancermentioning

confidence: 99%

Natural products as promising modulators of breast cancer immunotherapy

Alqathama

2024

Front. Immunol.

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Breast cancer (BC) is the most common malignancy among women and is considered a major global health challenge worldwide due to its high incidence and mortality rates. Treatment strategies for BC is wide-ranging and include surgery, radiotherapy, chemotherapy, targeted hormonal therapy and immunotherapy. Immunotherapy has gained popularity recently and is often integrated as a component of personalized cancer care because it aims to strengthen the immune system and enable it to recognize and eradicate transformed cells. It has fewer side-effects and lower toxicity than other treatment strategies, such as chemotherapy. Many natural products are being investigated for a wide range of therapeutic pharmacological properties, such as immune system modulation and activity against infection, auto-immune disease, and cancer. This review presents an overview of the major immune response-related pathways in BC, followed by detailed explanation of how natural compounds can act as immunomodulatory agents against biomolecular targets. Research has been carried out on many forms of natural products, including extracts, isolated entities, synthetic derivatives, nanoparticles, and combinations of natural compounds. Findings have shown significant regulatory effects on immune cells and immune cytokines that lead to immunogenic cancer cell death, as well as upregulation of macrophages and CD+8 T cells, and increased natural killer cell and dendritic cell activity. Natural products have also been found to inhibit some immuno-suppressive cells such as Treg and myeloid-derived suppressor cells, and to decrease immunosuppressive factors such as TGF-β and IL-10. Also, some natural compounds have been found to target and hinder immune checkpoints such as PD-L1.

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Section: Tumor Immune Microenvironment and Breast Cancermentioning

confidence: 99%

Natural products as promising modulators of breast cancer immunotherapy

Alqathama

2024

Front. Immunol.

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“…CAR-NK cell therapy is another type of promising treatment for cancers [5][6][7]. One of the advantages of NK cells is a low risk of graft-versus-host disease (GVHD) and low toxicity [8,9]. NK cells are also good candidates for allogeneic cell therapy as they show independence to HLA-TCR recognition signaling of T cells [10].…”

Section: Introductionmentioning

confidence: 99%

CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo

Golubovskaya,

Sienkiewicz,

Sun

et al. 2023

IJMS

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Natural killer (NK) cells are cytotoxic lymphocytes that are critical for the innate immune system. Engineering NK cells with chimeric antigen receptors (CARs) allows CAR-NK cells to target tumor antigens more effectively. In this report, we present novel CAR mRNA-LNP (lipid nanoparticle) technology to effectively transfect NK cells expanded from primary PBMCs and to generate functional CAR-NK cells. CD19-CAR mRNA and BCMA-CAR mRNA were embedded into LNPs that resulted in 78% and 95% CAR expression in NK cells, respectively. BCMA-CAR-NK cells after transfection with CAR mRNA-LNPs killed multiple myeloma RPMI8226 and MM1S cells and secreted IFN-gamma and Granzyme B in a dose-dependent manner in vitro. In addition, CD19-CAR-NK cells generated with CAR mRNA-LNPs killed Daudi and Nalm-6 cells and secreted IFN-gamma and Granzyme B in a dose-dependent manner. Both BCMA-CAR-NK and CD19-CAR-NK cells showed significantly higher cytotoxicity, IFN-gamma, and Granzyme B secretion compared with normal NK cells. Moreover, CD19-CAR-NK cells significantly blocked Nalm-6 tumor growth in vivo. Thus, non-viral delivery of CAR mRNA-LNPs can be used to generate functional CAR-NK cells with high anti-tumor activity.

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Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

Gerashchenko,

Frolova,

Patysheva

et al. 2024

Advanced Biology

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Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno‐oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte activity against transformed cells, a tumor can escape immune surveillance and leverage chronic inflammation to maintain its own development. Research on antitumor immunity primarily focuses on the role of the tumor microenvironment, whereas the systemic immune response beyond the tumor site is described less thoroughly. Here, a comprehensive review of the formation of the immune profile in breast cancer patients is offered. The interplay between systemic and local immune reactions as self‐sustaining mechanism of tumor progression is described and the functional activity of the main cell populations related to innate and adaptive immunity is discussed. Additionally, the interaction between different functional levels of the immune system and their contribution to the development of the pro‐ or anti‐tumor immune response in BC is highlighted. The presented data can potentially inform the development of new immunotherapy strategies in the treatment of patients with BC.

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Advances in natural killer cell therapies for breast cancer

Cited by 8 publications

References 179 publications

Natural products as promising modulators of breast cancer immunotherapy

Natural products as promising modulators of breast cancer immunotherapy

CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo

Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

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