Discovery of two new actinobacteria, Micromonospora palythoicola sp. nov. and Streptomyces poriticola sp. nov., isolated from marine invertebrates.

Marine invertebrates represent an underexplored reservoir for actinobacteria, which are known to synthesize novel bioactive compounds. This study isolated 37 actinobacterial strains from five distinct marine invertebrate hosts, namely Chondrilla australiensis, Palythoa sp., Favia sp.

Optimization of anti-TIM3 chimeric antigen receptor with CD8α spacer and TNFR-based costimulation for enhanced efficacy in AML therapy.

CAR T cell therapy for AML remains limited due to the lack of a proper target without on-target off-tumor toxicity. TIM3 is a promising target due to its high expression on AML cells and absence in most normal hematopoietic cells. Previous reports have shown that each CAR component impacts CAR functionality.

Surface functionalization of virus-like particles via bioorthogonal click reactions for enhanced cell-specific targeting.

Surface functionalization of nano drug carriers allows for precise delivery of therapeutic molecules to the target site. This technique involves attaching targeting molecules to the nanoparticle surface, facilitating selective interaction. In this study, we engineered virus-like particles (VLPs) to enhance their targeting capabilities.

Development of a compact bidirectional promoter-driven dual chimeric antigen receptor (CAR) construct targeting CD19 and CD20 in the Sleeping Beauty (SB) transposon system.

Background: A bidirectional promoter-driven chimeric antigen receptor (CAR) cassette provides the simultaneous expression of two CARs, which significantly enhances dual antigen-targeted CAR T-cell therapy.

Methods: We developed a second-generation CAR directing CD19 and CD20 antigens, incorporating them in a head-to-head orientation from a bidirectional promoter using a single Sleeping Beauty transposon system. The efficacy of bidirectional promoter-driven dual CD19 and CD20 CAR T cells was determined in vitro against cell lines expressing either, or both, CD19 and CD20 antigens.

Incorporating IL7 receptor alpha signaling in the endodomain of B7H3-targeting chimeric antigen receptor T cells mediates antitumor activity in glioblastoma.

CAR-T-cell therapy has shown promise in treating hematological malignancies but faces challenges in treating solid tumors due to impaired T-cell function in the tumor microenvironment. To provide optimal T-cell activation, we developed a B7 homolog 3 protein (B7H3)-targeting CAR construct consisting of three activation signals: CD3ζ (signal 1), 41BB (signal 2), and the interleukin 7 receptor alpha (IL7Rα) cytoplasmic domain (signal 3). We generated B7H3 CAR-T cells with different lengths of the IL7Rα cytoplasmic domain, including the full length (IL7R-L), intermediate length (IL7R-M), and short length (IL7R-S) domains, and evaluated their functionality in vitro and in vivo.

Effects of Cannabidiol on the Functions of Chimeric Antigen Receptor T Cells in Hematologic Malignancies.

CD19-chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy for cancer treatment that has shown remarkable clinical responses, leading to approval by the FDA for relapsed and refractory B cell hematological malignancy treatment. Cannabidiol (CBD) is a nonpsychoactive cannabinoid compound that has been utilized as a palliative treatment in cancer patients due to its immunosuppressive properties. Currently, studies on using CBD during immunotherapy have gained increasing attention.

Effect of plant produced Anti-hIL-6 receptor antibody blockade on pSTAT3 expression in human peripheral blood mononuclear cells.

As a response to invasion by pathogens, the secretion of interleukin 6 (IL-6) which is a cytokine, activates IL-6/JAKs/STAT3 intracellular signaling via., phosphorylation. Over expression of pSTAT3 induces IL-6 positive feedback loop causing cytokine release syndrome or cytokine storm.

A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy.

Hodgkin's lymphoma and anaplastic large cell lymphoma, especially relapsed or refractory diseases, could recently be cured by CD30-targeted immunotherapy. However, the CD30 antigen releases the soluble ectodomain of CD30, which might obscure the targeted therapy. Therefore, the membrane epitope of CD30 (mCD30), left on the cancer cells, might be a prospective target for lymphoma treatment.

Improving cytokine-induced killer cell expansion using a gas-permeable culture method for clinical-scale production.

Background: Cytokine-induced killer (CIK) cells are a heterogeneous group of immune cells that exert potent MHC-unrestricted cytotoxicity toward various cancer cells in both solid and hematological malignancies.

Objective: The purposes of this study were to compare the expansion and characteristics of cytokine-induced killer cells between a standard culture method and a gas-permeable culture method and to develop a clinical-scale expansion protocol for cytokine-induced killer cells using a gas-permeable culture method.

Methods: We compared the absolute cell number, fold change, cell subsets, activation markers, cytokine concentrations, and cytotoxicity toward myeloid leukemia cell lines between cytokine-induced killer cells expanded using two different culture methods.

Novel xeno-free and serum-free culturing condition to improve piggyBac transposon-based CD19 chimeric antigen receptor T-cell production and characteristics.

Background Aims: Chimeric antigen receptor (CAR) T cell is a novel therapy for relapse and refractory hematologic malignancy. Characteristics of CAR T cells are associated with clinical efficacy and toxicity. The type of serum supplements used during cultivation affects the immunophenotype and function of viral-based CAR T cells.

An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment.

Adoptive cellular therapy with chimeric antigen receptor (CAR) T cells has emerged as a potential novel treatment for various cancers. In this study, we have generated CAR T cells targeting mucin-1 (MUC1), which is an aberrantly glycosylated antigen overexpressed on breast cancer cells. Two different signaling domains, including CD28 and 41BB, were incorporated and directly compared the superiority of different costimulatory signals.

Triple-negative breast cancer influences a mixed M1/M2 macrophage phenotype associated with tumor aggressiveness.

Triple-negative breast cancer (TNBC) is characterized by excessive accumulation of tumor-infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs consist of a heterogeneous population with high plasticity and are associated with tumor aggressiveness and poor prognosis. Moreover, breast cancer cells can secrete factors that influence TAM polarization.

MicroRNA-mediated metabolic reprogramming of chimeric antigen receptor T cells.

Advances made in chimeric antigen receptor (CAR) T cell therapy have revolutionized the treatment and management of certain cancers. Currently, B cell malignancies have been among the few cancers to which CAR T cells have shown persistent and resilient anti-tumor responses. A growing body of evidence suggests that the persistence of CAR T cells within patients following infusion is linked to the mitochondrial fitness of the CAR T cell, which could affect clinical outcomes.

Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats.

Background: ECa 233 is a standardized extract of C. asiatica containing the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.

Blocking of Type 1 Angiotensin II Receptor Inhibits T-lymphocyte Activation and IL-2 Production.

Background/aim: Novel information on the role of endogenous compounds in regulating physiological and pathological process are of interest, as it may lead to the development of better strategies for disease management. The role of angiotensin II and the signaling of type 1 angiotensin II receptor (AGT1R) in T-lymphocyte activation and interleukin-2 (IL-2) production are largely unknown.

Materials And Methods: Jurkat T-cells were treated with AGT1R inhibitor candesartan and stimulated with phorbol myristate acetate (PMA) and ionomycin.

CAR T cell therapy for breast cancer: harnessing the tumor milieu to drive T cell activation.

Background: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site.

Functional aortic stiffness: role of CD4(+) T lymphocytes.

The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1(-/-) mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling.

Angiotensin II Increases Cancer Stem Cell-like Phenotype in Lung Cancer Cells.

Background: Cancer stem cells (CSCs) have been proposed as important players in cancer progression, metastasis, and chemotherapeutic resistance in many cancers, including lung cancer. However, effects of the endogenous substance angiotensin II (ANG II) on cancer stem cell-like phenotype in lung cancer are largely unknown.

Materials And Methods: Human lung cancer cells were treated with non-cytotoxic concentrations of ANG II.

Effect of lysyl oxidase inhibition on angiotensin II-induced arterial hypertension, remodeling, and stiffness.

It is well accepted that angiotensin II (Ang II) induces altered vascular stiffness through responses including both structural and material remodeling. Concurrent with remodeling is the induction of the enzyme lysyl oxidase (LOX) through which ECM proteins are cross-linked. The study objective was to determine the effect of LOX mediated cross-linking on vascular mechanical properties.

Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening.

Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (mAbCD25).