B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors.

Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen presentation pathway, making them a potential "off-the-shelf" cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation.

Preconditioning of radiotherapy enhances efficacy of B7-H3-CAR-T in treating solid tumor models.

Aims: Limited efficacy of chimeric antigen receptor T (CAR-T) cells in treating solid tumors is largely due to the antigen heterogeneity and immunosuppressive tumor microenvironment (TME). B7-H3 is over-expressed in most kind of solid tumors, making it a promising target for cancer treatment. This study aims to explore the effect of B7-H3-CAR-T therapy combined with radiotherapy in treating solid tumor models.

CD7 protein plays a crucial role in T cell infiltration in tumors.

CD7 protein as a target is being used to treat CD7 lymphoma; however, the role of CD7 in the hematopoietic system remains largely unknown. Therefore, we evaluated the effects of CD7 KO in mice. The differentiation of the hematopoietic system in the bone marrow and the number of various cell types in the thymus and spleen did not differ between CD7 KO and WT mice.

B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia.

Background And Aims: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells.

RPRM deletion preserves hematopoietic regeneration by promoting EGFR-dependent DNA repair and hematopoietic stem cell proliferation post ionizing radiation.

Reprimo (RPRM), a target gene of p53, is a known tumor suppressor. DNA damage induces RPRM, which triggers p53-dependent G2 arrest by inhibiting cyclin B1/Cdc2 complex activation and promotes DNA damage-induced apoptosis. RPRM negatively regulates ataxia-telangiectasia mutated by promoting its nuclear-cytoplasmic translocation and degradation, thus inhibiting DNA damage.

Nanobody-based anti-CD22-chimeric antigen receptor T cell immunotherapy exhibits improved remission against B-cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 can achieve impressive clinical remission rates in the treatment of B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia. However, relapse after CD19-CAR T treatment remains a major issue, with CD19 antigen-negative relapse being one of the main reasons. CD22, another antigen expressed in a B-cell lineage-specific pattern, is retained following CD19 loss.

Zkscan3 affects erythroblast development by regulating the transcriptional activity of GATA1 and KLF1 in mice.

ZKSCAN3 encodes a zinc-finger transcription factor that regulates the expression of important genes and plays a significant role in tumor development, pathogenesis, and metastasis. However, its biological functions under normal physiological conditions remain largely unknown. In our previous studies, using flow cytometry, we found that the deletion of Zkscan3 may cause abnormal erythropoiesis.

Chimeric antigen receptor T cells derived from CD7 nanobody exhibit robust antitumor potential against CD7-positive malignancies.

The great success of chimeric antigen receptor T (CAR-T)-cell therapy in B-cell malignancies has significantly promoted its rapid expansion to other targets and indications, including T-cell malignancies and acute myeloid leukemia. However, owing to the life-threatening T-cell hypoplasia caused by CD7-CAR-T cells specific cytotoxic against normal T cells, as well as CAR-T cell-fratricide caused by the shared CD7 antigen on the T-cell surface, the clinical application of CD7 as a potential target for CD7 malignancies is lagging. Here, we generated T cells using an anti-CD7 nanobody fragment coupled with an endoplasmic reticulum/Golgi retention domain and demonstrated that these cells transduced with CD7-CAR could prevent fratricide and achieve expansion.

MUC1-Tn-targeting chimeric antigen receptor-modified Vγ9Vδ2 T cells with enhanced antigen-specific anti-tumor activity.

Chimeric antigen receptor (CAR) αβ T cell adoptive immunotherapy has shown great promise for improving cancer treatment. However, there are several hurdles to overcome for the wide clinical application of CAR-αβ T cells therapy, including side effects and a limited T cells source from cancer patients. Therefore, we sought to identify an alternative T cell subset that could avoid these limitations and improve the effectiveness of CAR-T immunotherapy.

A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies; however, designing CARs for T-cell based diseases remain a challenge since most target antigens are shared between normal and malignant cells, leading to CAR-T cell fratricide. CD7 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL), but it is not expressed in one small group of normal T lymphocytes. Here, we constructed monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using the CD7 nanobody VHH6 sequences from our laboratory.

Effects of CSF1R-targeted chimeric antigen receptor-modified NK92MI & T cells on tumor-associated macrophages.

Tumor immunotherapy has shown great progress for the treatment of cancer; however, both endogenous and exogenous T cells are inhibited by the immunosuppressive tumor microenvironment. Tumor-associated macrophages (TAMs) in the microenvironment play pivotal and complex roles in tumor development and progression. Macrophages are categorized as M1 and M2 types.

La/SSB chimeric autoantibody receptor modified NK92MI cells for targeted therapy of autoimmune disease.

It has been long sought to specifically eliminate B-cell clones that generate autoreactive antibodies, while sparing the immune system when combating autoimmune disease. Although it was impossible to achieve this goal before, newly developed techniques have made it feasible today. Autoantibodies against La/SSB were involved in several autoimmune diseases.

Gene-modified NK-92MI cells expressing a chimeric CD16-BB-ζ or CD64-BB-ζ receptor exhibit enhanced cancer-killing ability in combination with therapeutic antibody.

Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells.

Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells.

Various CD7-targeting immunotoxins have been tested for its potential in treating CD7+ malignant patients but none of those immunotoxins was approved clinically because of lacking enough efficacy and safety. Here we successfully constructed the monovalent and bivalent CD7 nanobody-based immunotoxins PG001 and PG002, both conjugated with a truncated derivative of Pseudomonas exotoxin A respectively. The prokaryotic system expressed immunotoxins not only maintained their binding specificity for CD7-positive cells with a Kd of 16.

Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization.

Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a co-receptor for growth factors and chemokines and is a molecular marker associated with the epithelial-mesenchymal transition during development and carcinogenesis. In this study, we generated two specific mouse anti-human CD138 monoclonal antibodies (mAbs, clone ID: 480CT5.4.

HMGB1 Promotes Mitochondrial Dysfunction-Triggered Striatal Neurodegeneration via Autophagy and Apoptosis Activation.

Impairments in mitochondrial energy metabolism are thought to be involved in many neurodegenerative diseases. The mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces striatal pathology mimicking neurodegeneration in vivo. Previous studies showed that 3-NP also triggered autophagy activation and apoptosis.

Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma.

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab-CD3), showed great performance in clinical treatment.

The zinc finger transcription factor ZKSCAN3 promotes prostate cancer cell migration.

In our previous studies, ZKSCAN3 was demonstrated to be over-expressed in invasive colonic tumor cells and their liver metastases, but minimally expressed in adjacent non-transformed tissues. Further preliminary data showed that ZKSCAN3 was expressed in a majority of prostate cancer patient samples, but not in normal prostate tissues. Moreover, the ZKSCAN3 protein is highly expressed in the PC3 prostate cancer cell line, which has high metastatic potential, but little expression was observed in non-metastatic prostate cancer cell lines.

Endoplasmic reticulum stress markers and ubiquitin–proteasome pathway activity in response to a 200-km run.

Purpose: This study investigated whether a 200-km run modulates signaling pathways implicated in cellular stress in skeletal muscle, with special attention paid to the endoplasmic reticulum (ER) stress and to the activation of the ubiquitin-proteasome pathway.

Methods: Eight men ran 200 km (28 h 03 min ± 2 h 01 min). Two muscle biopsies were obtained from the vastus lateralis muscle 2 wk before and 3 h after the race.