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.

Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma.

Purpose: Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7-chimeric antigen receptor (CAR) T cells in patients with relapsed and refractory (R/R) T-ALL/LBL, as well as its manufacturing feasibility.

Patients And Methods: Preclinical phase was conducted in NPG mice injected with Luc+ GFP+CCRF-CEM cells. Open-label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T-cell infusion.

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.

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.

[Killing Effect of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line on CD7-Positive Hematological Malignant Cells].

Objective: To investigate the killing effect of NK-92MI cells modified by chimeric antigen receptor (CD7-CAR) and specifically targeting CD7 to CD7 hematological malignant cells.

Methods: Three types of hematological malignant tumor cells, including 5 cases of CD7 acute T-lymphoblastic leukemia (T-ALL), 10 cases of acute myeloid leukemia (AML) and 6 cases of T-cell lymphoma were collected, centrifuged, cultured and used to detect the expression levels of tumor cell surface targets; 7-AAD, CD56-APC, CD3-FITC, IgG Fc-PE flow cytometry were used to detected the transfection efficiency of NK-92MI and CD7-CAR-NK-92MI cells, killing efficiencies of CD7-CAR-NK-92MI cells to CD7 hematological tumor cells in vitro were determined by flow cytometry using PE Annexin V Apoptosis Detection Kit. Secretion differences of NK-92MI and CD7-CAR-NK-92MI cytokines interleukin (IL)-2, interferon (IFN)-γ, and granzyme B detection were estimated by using CBA kit.

Decitabine enhances cytotoxic effect of T cells with an anti-CD19 chimeric antigen receptor in treatment of lymphoma.

CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy.

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.

Erratum: First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia.

[This corrects the article on p. 1083 in vol. 8, PMID: 30034945.

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia.

CAR T cells have shown clinical efficacy for acute lymphoblastic leukemia, but this therapy has not been effective for acute myeloid leukemia (AML), and other treatment options are needed. Theoretically, CAR-NK cells have a more favorable toxicity profile compared to CAR T cells, especially in avoiding adverse effects such as cytokine release syndrome. However, the clinical evidence for this has not yet been reported.

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.

Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells.

Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines.

First BAFF gene cloned from an aquatic mammal.

The finless porpoise (Neophocaena phocaenoides) is one of the smallest cetacean species. Research into the immune system of the finless porpoise is essential to the protection of this species, but, to date, no genes coding for proteins from the tumor necrosis factor family (TNF family) have yet been reported from finless porpoises. The TNF B cell activating factor (BAFF) is critical to B cell survival, proliferation, maturation, and immunoglobulin secretion and to T cell activation.

Molecular structure, expression analysis and functional characterization of APRIL (TNFSF13) gene in bat (Vespertilio superans Thomas).

A proliferation-inducing ligand (APRIL) is a novel member of the tumor necrosis factor (TNF) superfamily, which is involved in immune regulation. In the present study, the full-length cDNA of APRIL (designated bAPRIL) from bat was cloned using RT-PCR and its biological activities have been characterized. The open reading frame (ORF) of this cDNA consists of 753 bases, encoding a protein of 250 amino acids.

Molecular cloning, expression, bioinformatics analysis and bioactivity characterization of TNF13B (BAFF) gene in bat (Vespertilio superans Thomas).

B cell activating factor (BAFF) belonging to the tumor necrosis factor (TNF) family is critical to B cell survival, proliferation, maturation, and immunoglobulin secretion and to T cell activation. In the present study, the full-length cDNA of BAFF (designated bBAFF) from the bat (Vespertilio superans Thomas) was cloned using RT-PCR and rapid amplification of cDNA ends (RACE) techniques. The full-length cDNA of bBAFF consists of 986 bases including an 873 bp open reading frame encoding 290 amino acids.

The first BAFF gene cloned from the cartilaginous fish.

B-cell activating factor (BAFF), a member of the TNF family, is critical to the survival, proliferation, maturation, and differentiation of B-cells. In the present study, a CpBAFF was amplified from the white-spotted catshark (Chiloscyllium plagiosum) using RT-PCR and RACE (rapid amplification of cDNA end) techniques. To our knowledge, this is the first report of any BAFF gene being cloned from a cartilaginous fish.

Molecular cloning, bioinformatics analysis and functional characterization of B-cell activating factor in goat (Capra hircus).

B-cell activating factor of the TNF family (BAFF) induces B cell survival, proliferation, immunoglobulin secretion and has a role in enhancing immune responses. In the present study, we amplified the cDNA of goat (Capra hircus) BAFF (designated gBAFF) from spleen by reverse transcription-PCR (RT-PCR). The open reading frame (ORF) of gBAFF covers 843 bp encoding 280 amino acids, with a 152-aa mature peptide.