natural killer cell therapy / Xinxiang Medical University - LARVOL DELTA

Phenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy. (PubMed, Breast Cancer Res) - "These findings were validated in an independent cohort of 15 patients during 16-month follow-up. Overall, we identified a distinct immuno-suppressive TINK cell group, featuring IL10 + secreting and SELL expression with a strong relation to poor survival prognosis in TNBC patients post-NATI."

Biomarker • Checkpoint inhibition • IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL10 • NCAM1 • SELL

CAR-NK cells with dual targeting of PD-L1 and MICA/B in lung cancer tumor models. (PubMed, BMC Cancer) - "We confirmed that expression of dtCAR enhanced NK92-cell activation and killing in vitro and in vivo, which provides a novel immunotherapeutic strategy for using NK-tailored CAR-engineered NK92 cells to treat human lung cancer."

IO biomarker • Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • NKG2D

Enhanced effect of radiofrequency ablation on HCC by siRNA-PD-L1-endostatin Co-expression plasmid delivered. (PubMed, Transl Oncol) - "There was also a notable rise in T and NK cell populations in the spleen. In conclusion, combining RFA with siRNA-PD-L1-endostatin delivered by attenuated Salmonella synergistically enhances anti-tumor effects, boosts the anti-tumor immune response, and improves RFA efficacy for HCC."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD86 • GZMB • PD-L1

Enhanced Efficacy of Radiation Therapy against Glioblastoma by Attenuated Salmonella Carrying Co-Expression Plasmids with siRNA-PD-L1 and Endostatin. (PubMed, Curr Cancer Drug Targets) - "These findings highlight the ability of attenuated Salmonella carrying siR-NA-PD-L1 and co-expressing endostatin plasmids to effectively modulate PD-L1 and VEGF expression, thus strengthening the anti-tumor immune response in GBM-bearing mice subjected to radiation therapy. This combination therapy approach holds promise as a potential avenue for improving the efficacy of radiation therapy in the treatment of glio-blastoma."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CASP3 • CCND1 • CD4 • CD8 • MMP2 • PCNA • PD-L1 • STAT3

Lactate: a rising star in tumors and inflammation. (PubMed, Front Immunol) - "Lactate exerts immunosuppressive effects by regulating the functions of various immune cells (such as natural killer cells, T cells, dendritic cells, and monocytes) and its role in macrophage polarization and myeloid-derived suppressor cell (MDSC) differentiation in the tumor microenvironment...Factors such as cell types, transcriptional regulators, ionic mediators, and the microenvironment all contribute to the diverse functions lactate exhibits. Herein, we reviewed the pleiotropic effects of lactate on the regulation of various functions of immune cells in the tumor microenvironment and under inflammatory conditions, which may help to provide new insights and potential targets for the diagnosis and treatment of inflammatory diseases and malignancies."

Journal • Review • Infectious Disease • Oncology • CD8

Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic. (PubMed, J Immunol) - "Previous studies have demonstrated polymorphism at the 72nd amino acid of the NKG2D on human NK cells, with NKG2D72Thr exhibiting a superior activation effect on NK cells compared with NKG2D72Ala. We confirmed this conclusion also applies to NK-92 cells by in vitro cytotoxicity experiments. Therefore, reducing the immunoreactivity and immunogenicity of CAR-NK92 and directly switching NK-92 bearing NKG2D72Ala to NKG2D72Thr represent pressing challenges in realizing NK-92 cells as qualified universal off-the-shelf cellular therapeutics."

Journal • Oncology • NKG2D

Delivery of SiRNA-PD-L1 by attenuated Salmonella in combination with oxaliplatin in a hepatocellular carcinoma mouse model. (PubMed, Int Immunopharmacol) - "Moreover, the combination therapy increased the activation of T cells and the number of T lymphocytes and NK cells in the spleens of the mice and improved the overall antitumour immune response in the mice. Our results confirmed that attenuated Salmonella harbouring siRNA-PD-L1 combined with oxaliplatin had a significant antitumour effect and did not increase the incidence of toxic side effects, providing a theoretical reference for addressing oxaliplatin tolerance in the treatment of hepatocellular carcinoma."

Combination therapy • IO biomarker • Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CASP3 • PD-L1

Preliminary results from a phase I expansion study of ZG005, a bispecific antibody targeting TIGIT and PD-1, as monotherapy in patients with advanced solid tumors. (ASCO 2024) - "Background: ZG005, a PD-1 and TIGIT dual-specific antibody, is a promising immunotherapy for tumors as blocking these two pathways could synergistically activate T cells and enhance the anti-tumor activity of NK cells. ZG005 has demonstrated a tolerable safety profile and encouraging anti-tumor activity during the FIH study. Expansion cohorts in specific advanced solid tumors are underway to warrant further development."

Clinical • Metastases • Monotherapy • P1 data • Biliary Cancer • Cervical Cancer • Cholangiocarcinoma • Dyslipidemia • Endocrine Cancer • Gastrointestinal Cancer • Hepatology • Hypertriglyceridemia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • TIGIT

A novel MICA/B-targeted chimeric antigen receptor augments the cytotoxicity of NK cells against tumor cells. (PubMed, Biochem Biophys Res Commun) - "The engineered NK cells exhibited significantly enhanced cytotoxicity against various MICA/B-expressing tumor cells and were not inhibited by NKG2D antibody or NKG2D-Fc fusion protein, indicating no interference with NKG2D-MICA/B binding. Therefore, the developed 1D5-CAR could be combined with NKG2D-CAR to further improve the obstacles caused by MICA/B shedding."

Journal • Tumor cell • Oncology • Solid Tumor • MICA • MICB • NKG2D

Identification of mitophagy-related hub genes during the progression of spinal cord injury by integrated multinomial bioinformatics analysis. (PubMed, Biochem Biophys Rep) - "In total, SKP1 and BAP1 were identified as hub genes of mitophagy-related DEGs during SCI development and regulatory T cells (Tregs)/resting NK cells/activated mast cells may play an essential role in the progression of SCI...Then, the mRNA expression levels of BAP1 and SKP1 were detected in the injured sites of spinal cord of SD rats at 6 h and 72 h after injury using RT-qPCR, and found that the level were decreased. Therefore, the pathways of mitophagy are downregulated during the pathophysiology of SCI, and SKP1 and BAP1 could be accessible targets for diagnosing and treating SCI."

Journal • CNS Disorders • Orthopedics • BAP1 • SNHG16

NK Cells Treatment for COVID-19 (clinicaltrials.gov) - P1 | N=2 | Completed | Sponsor: Xinxiang medical university | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

The SpyCatcher-SpyTag interaction mediates tunable anti-tumor cytotoxicity of NK cells. (PubMed, Mol Immunol) - "The results demonstrated that the increasing number of SpyTags effectively enhanced the cytotoxicity of SpyCAR-NK92 cells against target cells. The development of SpyCAR with tunable cytotoxicity provides a novel strategy for CAR-based tumor immunotherapies."

Journal • Oncology

Maprotiline Prompts an Antitumour Effect by Inhibiting PD-L1 Expression in Mice with Melanoma. (PubMed, Curr Mol Pharmacol) - "Our research findings suggest that maprotiline enhances the antitumour immune response in mouse melanoma by inhibiting PD-L1 expression. This study may discover a new PD-L1 inhibitor, providing a novel therapeutic option for the clinical treatment of tumours."

IO biomarker • Journal • Preclinical • CNS Disorders • Depression • Melanoma • Oncology • Psychiatry • Solid Tumor • CD4 • CD8

Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement. (PubMed, Cell Death Discov) - "Additionally, the combination treatment increased the ratios of CD4 T, CD8 T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • CD8 • PD-L1

Intrinsic and extrinsic factors determining natural killer cell fate: Phenotype and function. (PubMed, Biomed Pharmacother) - "This review targets the potential of NK cell metabolism, cellular molecules, regulatory genes, and other mechanisms involved in immune regulation. We further discuss immune-mediated tumor therapy, which is the trend of current research."

Journal • Review • Oncology

Regulation of the tumor immune microenvironment by cancer-derived circular RNAs. (PubMed, Cell Death Dis) - "Immune cells are the most abundant cellular TME components, and they have profound toxicity to cancer cells. This review summarizes circRNA regulation of immune cells, including T cells, natural killer cells, and macrophages; highlights the impact of circRNAs on tumor progression, treatment, and prognosis; and indicates new targets for tumor immunotherapy."

Journal • Review • Oncology

Engagement of an optimized lentiviral vector enhances the expression and cytotoxicity of CAR in human NK cells. (PubMed, Mol Immunol) - "Therefore, infection with a single-promoter pCDHsp lentivector is recommended to prepare CAR-engineered NK cells. This research helps to optimize the production of CAR-NK cells and enhance their functional activity, to provide CAR-NK cell products with better and more uniform quality."

IO biomarker • Journal • Viral vector • Infectious Disease • Oncology • NKG2D

High expression of B4GALT1 is associated with poor prognosis in acute myeloid leukemia. (PubMed, Front Genet) - "In addition, B4GALT1 expression was positively correlated with the infiltration levels of macrophages, regulatory T-cell (Tregs), and Th17 cells; in contrast, B4GALT1 expression was negatively correlated with the infiltration levels of T helper cells, Mast cells, and NK cells. In conclusion, our study shows that B4GALT1 may play a vital role in the occurrence of LAML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer. (PubMed, Front Mol Biosci) - "In most types of tumors, the expression of USP45 was positively correlated with many immune checkpoint molecules and immune regulators such as PD-L1, while negatively correlated with the infiltration levels of NK cells, Th1 cells, macrophages, and dendritic cells in the tumor microenvironment. Finally, we constructed the ceRNA regulatory network, protein-protein interaction network and downstream regulatory network for USP45 in different types of tumors. Our study firstly explored the putative oncogenic role of USP45 in pan-cancer, and provided insights for further investigation of USP45."

IO biomarker • Journal • Pan tumor • Immune Modulation • Inflammation • Inflammatory Arthritis • Oncology • Targeted Protein Degradation • PD-L1

Cytokine Release Syndrome After Modified CAR-NK Therapy in an Advanced Non-small Cell Lung Cancer Patient: A Case Report. (PubMed, Cell Transplant) - "However, we observed occurrence of cytokine release syndrome (CRS), a rare and unexpected side effect, never reported before during CAR-NK therapy. Here, we provide a detailed report of the patient's case, emphasize on the need to pay attention to CRS in NK cell therapy, and suggest improvements that will minimize potential toxicity."

Cytokine release syndrome • Journal • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A chimeric switch-receptor PD1-DAP10-41BB augments NK92-cell activation and killing for human lung Cancer H1299 Cell. (PubMed, Biochem Biophys Res Commun) - "NK cell immunotherapy however always remains variable...More importantly, in the solid tumor cell H1299-bearing mice model, the CSR-modified NK92 cells significantly inhibited tumor growth. Collectively, we demonstrated that expression of PD1-DAP10-41BB augmented NK92-cell activation and killing in vitro and in vivo, which provides a considerable avenue of using NK-tailored chimeric receptor engineered NK92 cells to treat a wide range of solid tumors."

IO biomarker • Journal • Immune Modulation • Inflammation • Lung Cancer • Oncology • Solid Tumor • PD-1

NK Cells Treatment for COVID-19 (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Xinxiang medical university | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CD4

D-MT prompts the anti-tumor effect of oxaliplatin by inhibiting IDO expression in a mouse model of colon cancer. (PubMed, Int Immunopharmacol) - "Herein, an IDO inhibitor, D-MT (indoximod, 1-Methyl-D-tryptophan), was combined with oxaliplatin to treat colon cancer in mice. More importantly, the combination treatment increased the ratios of CD4 T, CD8 T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues. This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • IDO1

NK Cells Treatment for COVID-19 (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Xinxiang medical university; Trial completion date: Dec 2020 ➔ Dec 2022; Trial primary completion date: Sep 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CD4 • PCR