International Journal of Molecular Sciences

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3 pages, 160 KiB

Open AccessEditorial

Advances in Targeted Immunotherapy in Cancers

by Na Luo

Int. J. Mol. Sci. 2023, 24(24), 17475; https://doi.org/10.3390/ijms242417475 - 14 Dec 2023

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Abstract

Immunotherapy has revolutionized cancer treatment, especially the emergence of immune checkpoint inhibitors (ICIs), which has been considered as a significant breakthrough in cancer therapy [...] Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

Research

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20 pages, 3311 KiB

Open AccessArticle

Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4

by Alaa Alsalloum, Julia Shevchenko, Marina Fisher, Julia Philippova, Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Saleh Alrhmoun, Julia Lopatnikova, Kurilin Vasily, Marina Volynets, Evgenii Zavjalov, Olga Solovjeva, Yasushi Akahori, Hiroshi Shiku, Alexander Silkov and Sergey Sennikov

Int. J. Mol. Sci. 2023, 24(20), 15134; https://doi.org/10.3390/ijms242015134 - 13 Oct 2023

Viewed by 1557

Abstract

TCR-like chimeric antigen receptor (CAR-T) cell therapy has emerged as a game-changing strategy in cancer immunotherapy, offering a broad spectrum of potential antigen targets, particularly in solid tumors containing intracellular antigens. In this study, we investigated the cytotoxicity and functional attributes of in [...] Read more.

TCR-like chimeric antigen receptor (CAR-T) cell therapy has emerged as a game-changing strategy in cancer immunotherapy, offering a broad spectrum of potential antigen targets, particularly in solid tumors containing intracellular antigens. In this study, we investigated the cytotoxicity and functional attributes of in vitro-generated T-lymphocytes, engineered with a TCR-like CAR receptor precisely targeting the cancer testis antigen MAGE-A4. Through viral transduction, T-cells were genetically modified to express the TCR-like CAR receptor and co-cultured with MAGE-A4-expressing tumor cells. Flow cytometry analysis revealed a significant surge in cells expressing activation markers CD69, CD107a, and FasL upon encountering tumor cells, indicating robust T-cell activation and cytotoxicity. Moreover, immune transcriptome profiling unveiled heightened expression of pivotal T-effector genes involved in immune response and cell proliferation regulation. Additionally, multiplex assays also revealed increased cytokine production and cytotoxicity driven by granzymes and soluble Fas ligand (sFasL), suggesting enhanced anti-tumor immune responses. Preliminary in vivo investigations revealed a significant deceleration in tumor growth, highlighting the therapeutic potential of these TCR-like CAR-T cells. Further investigations are warranted to validate these revelations fully and harness the complete potential of TCR-like CAR-T cells in overcoming cancer’s resilient defenses. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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16 pages, 4045 KiB

Open AccessArticle

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

by Tatyana Belovezhets, Sergey Kulemzin, Olga Volkova, Alexander Najakshin, Alexander Taranin and Andrey Gorchakov

Int. J. Mol. Sci. 2023, 24(4), 3698; https://doi.org/10.3390/ijms24043698 - 12 Feb 2023

Cited by 1 | Viewed by 2402

Abstract

Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved [...] Read more.

Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved by the FDA. Despite the spectacular rates of complete remission in r/r ALL and NHL patients, a significant proportion of patients still relapse, frequently with the CD19 low/negative tumor phenotype. To address this issue, additional B cell surface molecules such as CD20 were proposed as targets for CAR T cells. Here, we performed a side-by-side comparison of the activity of CD20-specific CAR T cells based on the antigen-recognition modules derived from the murine antibodies, 1F5 and Leu16, and from the human antibody, 2F2. Whereas CD20-specific CAR T cells differed from CD19-specific CAR T cells in terms of subpopulation composition and cytokine secretion, they displayed similar in vitro and in vivo potency. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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17 pages, 2084 KiB

Open AccessArticle

Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors

by Cédric Mahiat, Benoît Bihin, Fabrice Duplaquet, Claudia Stanciu Pop, Michael Dupont, Thierry Vander Borght, Benoît Rondelet, Jean Vanderick, Bénédicte André, Lionel Pirard and Sebahat Ocak

Int. J. Mol. Sci. 2023, 24(4), 3618; https://doi.org/10.3390/ijms24043618 - 10 Feb 2023

Cited by 5 | Viewed by 1984

Abstract

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + [...] Read more.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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Review

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26 pages, 1821 KiB

Open AccessReview

Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy

by Kyeonghee Shim, Hyein Jo and Dooil Jeoung

Int. J. Mol. Sci. 2023, 24(19), 14679; https://doi.org/10.3390/ijms241914679 - 28 Sep 2023

Cited by 1 | Viewed by 1833

Abstract

In the last few decades, RNA-based drugs have emerged as a promising candidate in the treatment of various diseases. The introduction of messenger RNA (mRNA) as a vaccine or therapeutic agent enables the production of almost any functional protein/peptide. The key to applying [...] Read more.

In the last few decades, RNA-based drugs have emerged as a promising candidate in the treatment of various diseases. The introduction of messenger RNA (mRNA) as a vaccine or therapeutic agent enables the production of almost any functional protein/peptide. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes and lipid nanoparticles (LNPs) have been exploited as promising vehicles for drug delivery. This review discusses the feasibility of exosomes and LNPs as vehicles for mRNA delivery. Cancer/testis antigens (CTAs) show restricted expression in normal tissues and widespread expression in cancer tissues. Many of these CTAs show expression in the sera of patients with cancers. These characteristics of CTAs make them excellent targets for cancer immunotherapy. This review summarizes the roles of CTAs in various life processes and current studies on mRNAs encoding CTAs. Clinical studies present the beneficial effects of mRNAs encoding CTAs in patients with cancers. This review highlight clinical studies employing mRNA-LNPs encoding CTAs. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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29 pages, 1028 KiB

Open AccessReview

Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review

by Yujun Zhang, Jingjing Song, Yiwei Zhang, Ting Li, Jie Peng, Haonan Zhou and Zhen Zong

Int. J. Mol. Sci. 2023, 24(1), 334; https://doi.org/10.3390/ijms24010334 - 25 Dec 2022

Cited by 5 | Viewed by 3302

Abstract

Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for [...] Read more.

Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for their high mortality and morbidity. Increasing research suggests that NETs contribute to the progression and metastasis of digestive tract tumors, among them gastric, colon, liver, and pancreatic cancers. This article explores the formation of NETs and reviews the role that NETs play in the gastrointestinal oncologic microenvironment, tumor proliferation and metastasis, tumor-related thrombosis, and surgical stress. At the same time, we analyze the qualitative and quantitative detection methods of NETs in recent years and found that NETs are specific markers of coronavirus disease 2019 (COVID-19). Then, we explore the possibility of NET inhibitors for the treatment of digestive tract tumor diseases to provide a new, efficient, and safe solution for the future therapy of gastrointestinal tumors. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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14 pages, 719 KiB

Open AccessReview

PTPN2 in the Immunity and Tumor Immunotherapy: A Concise Review

by Jiachun Song, Jinxin Lan, Jiaping Tang and Na Luo

Int. J. Mol. Sci. 2022, 23(17), 10025; https://doi.org/10.3390/ijms231710025 - 2 Sep 2022

Cited by 6 | Viewed by 4737

Abstract

PTPN2 (protein tyrosine phosphatase non-receptor 2), also called TCPTP (T cell protein tyrosine phosphatase), is a member of the PTP family signaling proteins. Phosphotyrosine-based signaling of this non-transmembrane protein is essential for regulating cell growth, development, differentiation, survival, and migration. In particular, PTPN2 [...] Read more.

PTPN2 (protein tyrosine phosphatase non-receptor 2), also called TCPTP (T cell protein tyrosine phosphatase), is a member of the PTP family signaling proteins. Phosphotyrosine-based signaling of this non-transmembrane protein is essential for regulating cell growth, development, differentiation, survival, and migration. In particular, PTPN2 received researchers’ attention when Manguso et al. identified PTPN2 as a cancer immunotherapy target using in vivo CRISPR library screening. In this review, we attempt to summarize the important functions of PTPN2 in terms of its structural and functional properties, inflammatory reactions, immunomodulatory properties, and tumor immunity. PTPN2 exerts synergistic anti-inflammatory effects in various inflammatory cells and regulates the developmental differentiation of immune cells. The diversity of PTPN2 effects in different types of tumors makes it a potential target for tumor immunotherapy. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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19 pages, 884 KiB

Open AccessReview

Rationale and Clinical Research Progress on PD-1/PD-L1-Based Immunotherapy for Metastatic Triple-Negative Breast Cancer

by Yifan Ren, Jialong Song, Xinyi Li and Na Luo

Int. J. Mol. Sci. 2022, 23(16), 8878; https://doi.org/10.3390/ijms23168878 - 10 Aug 2022

Cited by 8 | Viewed by 2740

Abstract

Metastatic triple-negative breast cancer (mTNBC), a highly aggressive and malignant tumor, currently lacks an effective treatment. There has been some progress in the treatment of mTNBC with programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) immunotherapy in recent years. The combination of PD-1/PD-L1 inhibitors with [...] Read more.

Metastatic triple-negative breast cancer (mTNBC), a highly aggressive and malignant tumor, currently lacks an effective treatment. There has been some progress in the treatment of mTNBC with programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) immunotherapy in recent years. The combination of PD-1/PD-L1 inhibitors with other therapies is a noteworthy treatment strategy. Immunotherapy in combination with chemotherapy or small-molecule inhibitors still faces many challenges. Additionally, there are some new immunotherapy targets in development. We aimed to further evaluate the effectiveness and usefulness of immunotherapy for treating mTNBC and to propose new immunotherapy strategies. This review explains the rationale and results of existing clinical trials evaluating PD-1/PD-L1 inhibitors alone or in combination for the treatment of mTNBC. For patients with aggressive tumors and poor health, PD-1/PD-L1 inhibitors, either alone or in combination with other modalities, have proven to be effective. However, more research is needed to explore more effective immunotherapy regimens that will lead to new breakthroughs in the treatment of mTNBC. Full article

(This article belongs to the Special Issue Advances in Targeted Immunotherapy in Cancers)

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