Current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment.

New York-esophageal cancer 1 (NY-ESO-1) belongs to the cancer testis antigen (CTA) family, and has been identified as one of the most immunogenic tumor-associated antigens (TAAs) among the family members. Given its ability to trigger spontaneous humoral and cellular immune response and restricted expression, NY-ESO-1 has emerged as one of the most promising targets for cancer immunotherapy. Cancer vaccines, an important element of cancer immunotherapy, function by presenting an exogenous source of TAA proteins, peptides, and antigenic epitopes to CD4 T cells major histocompatibility complex class II (MHC-II) and to CD8 T cells major histocompatibility complex class I (MHC-I).

Identification and assessment of TCR-T cells targeting an epitope conserved in SARS-CoV-2 variants for the treatment of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants.

Rapid identification of tumor-reactive T-cell receptors by RNA preamplification-based single-cell sequencing.

T-cell receptor (TCR)-transduced T (TCR-T) cell therapy has shown promising efficacy in the clinical treatment of malignant cancers. However, the populations covered by reported TCRs are still limited. Tumor infiltrating lymphocytes (TILs) are natural reservoirs of tumor-reactive T cells and TCRs.

Benefits of Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma.

The aim was to study the benefits and risks of anti-CD19 chimeric antigen receptor (CAR) T-cells in adults with B-cell lymphoma. From October 2015 to October 2021, we treated five patients with B-cell lymphoma, comprising two with mantle cell lymphoma, one case of Burkitt lymphoma, one case of diffuse large B-cell lymphoma, and one case of chronic lymphocytic leukemia/small lymphocytic lymphoma. The patients were given the FC regimen 5 days before the infusion of anti-CD19 CAR T-cells.

Molecular Expression Profile of Changes in Rat Acute Spinal Cord Injury.

Spinal cord injury (SCI) is a highly lethal and debilitating disease with a variety of etiologies. To date, there is no effective therapeutic modality for a complete cure. The pathological mechanisms of spinal cord injury at the molecular gene and protein expression levels remain unclear.

A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy.

T-cell therapy, usually with ex-vivo expansion, is very promising to treat cancer. Differentiation status of infused T cells is a crucial parameter for their persistence and antitumor immunity. Key phenotypic molecules are effective and efficient to analyze differentiation status.

An efficient method to identify virus-specific TCRs for TCR-T cell immunotherapy against virus-associated malignancies.

Adoptive transfer of T cells genetically engineered with a T cell receptor (TCR) is a promising cancer treatment modality that requires the identification of TCRs with good characteristics. Most T cell cloning methods involve a stringent singularization process, which necessitates either tedious hands-on operations or high cost. We present an efficient and nonstringent cloning approach based on existing techniques.

Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019.

Background: Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19.

Methods: In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.

Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways.

T cell exhaustion is an obstacle to immunotherapy for solid tumors. An understanding of the mechanism by which T cells develop this phenotype in solid tumors is needed. Here, hypoxia, a feature of the tumor microenvironment, causes T cell exhaustion (T) by inducing a mitochondrial defect.

Galectin-9 promotes a suppressive microenvironment in human cancer by enhancing STING degradation.

Galectin-9 (Gal-9) is known to enhance the expansion of myeloid-derived suppressor cells (MDSCs) in murine models. Its contribution to the expansion of MDSCs in human malignancies remain to be investigated. We here report that Gal-9 expression in nasopharyngeal carcinoma (NPC) cells enhances the generation of MDSCs (CD33CD11bHLA-DR) from CD33 bystander cells.

Glucosamine-6-Phosphate Isomerase 1 Promotes Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma.

Purpose: Reprogramming of metabolic pathways is a hallmark of the pathological changes that occur in cancer cells. Under physiological conditions, glucosamine-6-phosphate isomerase 1 (GNPDA1) promotes the conversion of the hexosamine system to the glycolytic pathway and may, therefore, affect energy metabolism. Low expression of GNPDA1 has been reported in normal liver tissues, however, analysis of the hepatocellular carcinoma (HCC) database in The Cancer Genome Atlas (TCGA) revealed that GNPDA1 was highly expressed in HCC tissues.

Osteoimmune Modulation and Guided Osteogenesis Promoted by Barrier Membranes Incorporated with S-Nitrosoglutathione (GSNO) and Mesenchymal Stem Cell-Derived Exosomes.

Background: The use of polycaprolactone (PCL) for bone defects in a clinical setting is limited due to a lack of bioactivity. Exosomes derived from mesenchymal stem cells (MSCs) have an important immunoregulatory potential and together with S-nitrosoglutathione (GSNO) they possess therapeutic potential for bone regeneration.

Materials And Methods: In this study, PCL was modified with GSNO and MSC-derived exosomes and the impact on macrophages and osteogenes is evaluated.

Synergy of GSK-J4 With Doxorubicin in KRAS-Mutant Anaplastic Thyroid Cancer.

Background: Anaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it.

Methods: Here, we used different concentrations of GSK-J4 or a combination of GSK-J4 and doxorubicin to treat human Cal-62, 8505C, and 8305C anaplastic thyroid cancer (ATC) cell lines.

High-throughput screening of functional deubiquitinating enzymes in autophagy.

Macroautophagy/autophagy, a eukaryotic homeostatic process that sequesters cytoplasmic constituents for lysosomal degradation, is orchestrated by a number of autophagy-related (ATG) proteins tightly controlled by post-translational modifications. However, the involvement of reversible ubiquitination in the regulation of autophagy remains largely unclear. Here, we performed a single-guide RNA-based screening assay to investigate the functions of deubiquitinating enzymes (DUBs) in regulating autophagy.

Phenotypic analysis of tumor-infiltrating lymphocytes from non-small cell lung cancer and their potential application for adoptive cell therapy.

Aim: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) has demonstrated clinical benefits in metastatic melanoma treatment. However, the clinical application of TILs produced by a widely used standard protocol from non-small cell lung cancer (NSCLC) can be quite challenging because of the limited clinical benefits. A comprehensive phenotypic knowledge of TILs obtained from NSCLC is important for the development and improvement of personalized TIL therapy for NSCLC patients.

Cancer immunotherapy with lymphocytes genetically engineered with T cell receptors for solid cancers.

Adoptive transfer of T cells genetically engineered with chimeric antigen receptors (CAR-T cells) have proven to be highly effective for treating CD19 B cell-derived hematologic malignancies. However, due to the lack of ideal tumor surface antigens, CAR-T cell therapy has limited success in treating solid tumors. T cells genetically engineered with T cell receptors (TCR-T cells) recognize intracellular and cell-surface antigens in the context of major histocompatibility complex (MHC) presentation and thus have the potential to access much more target antigens than CAR-T cells, providing great promise in treating solid tumors.

Expression of New York esophageal squamous cell carcinoma 1 and its association with Foxp3 and indoleamine-2,3-dioxygenase in microenvironment of nonsmall cell lung cancer.

Lung cancer is one of the most prevalent and fatal cancer worldwide. The traditional treatments including surgery, radiotherapy, chemotherapy and targeted therapy are not satisfactory because of severe side effects and/or relapse. Genetically engineered T-cell-based immunotherapy for malignant cancer shows promise in recent clinical trials.

Treatment of metastatic non-small cell lung cancer with NY-ESO-1 specific TCR engineered-T cells in a phase I clinical trial: A case report.

This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial.

LRRC25 Functions as an Inhibitor of NF-κB Signaling Pathway by Promoting p65/RelA for Autophagic Degradation.

Nuclear factor κB (NF-κB) is a family of critical transcription factors that play a critical role in innate immune responses and inflammation, yet the molecular mechanisms responsible for its tight regulation is not fully understood. In this study, we identified LRRC25, a member of leucine-rich repeat (LRR)-containing protein family, as a negative regulator in the NF-κB signaling pathway. Ectopic expression of LRRC25 impaired NF-κB activation, whereas knockout of LRRC25 potentiated NF-κB activation and enhanced the production of inflammatory cytokines.