Direct and Indirect Chimeric Antigen Receptor T-Cell Imaging with PET/MRI in a Tumor Xenograft Model.

Background Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored. Purpose To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors. Materials and Methods CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells.

Proteomics Analysis of Antitumor Activity of Ledeb. in Human Oral Squamous Cell Carcinoma Cells.

Oral cancer is a malignant neoplasm of oral cavity. It accounts for approximately 5% of all malignant tumors. Approximately 97% of all oral cancers are squamous cell carcinomas, followed by adenocarcinomas, and rarely malignant melanomas.

Odontogenic Differentiation-Induced Tooth Regeneration by L.

L. () has been used as an oriental phytomedicine to treat coldness of hands and feet in bone marrow injury. Hydroxyapatite is usually used for tooth regeneration.

Local adenoviral delivery of soluble CD200R-Ig enhances antitumor immunity by inhibiting CD200-β-catenin-driven M2 macrophage.

CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization.

IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.

Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient () BMT to understand why myeloid IDO limits the severity of GVHD.

Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging.

Introduction: Chimeric antigen receptor (CAR) T-cells have been recently developed and are producing impressive outcomes in patients with hematologic malignancies. However, there is no standardized method for cell trafficking and in vivo CAR T-cell monitoring. We assessed the feasibility of real-time in vivo 89Zr-p-Isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS, DFO) labeled CAR T-cell trafficking using positron emission tomography (PET).

Skewed Dendritic Cell Differentiation of MyD88-Deficient Donor Bone Marrow Cells, Instead of Massive Expansion as Myeloid-Derived Suppressor Cells, Aggravates GVHD.

Graft-versus-host disease (GVHD), a life-threatening complication after bone marrow transplantation (BMT), is induced by activation of alloreactive donor T cells. Our previous study demonstrated that transplantation of myeloid differentiation factor 88 (MyD88)-deficient knockout (KO) bone marrow (BM) resulted in aggravation of GVHD. Here, to understand the cellular mechanism, we performed longitudinal imaging and flow cytometric analyses followed by transcriptome and functional examination of donor MyD88-KO BM progenies in GVHD hosts, using a major histocompatibility complex-matched but minor histocompatibility antigen-mismatched C57BL/6→BALB.

Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen.

Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion.

Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60.

Minor histocompatibility antigens are MHC-bound peptides and contribute to the generation of allo-responses after allogeneic transplantation. H60 is a dominant minor H antigen that induces a strong CD8 T-cell response in MHC-matched allogeneic transplantation settings. Here, we report establishment of a TCR transgenic mouse line named J15, wherein T cells express TCRs specific for H60 in complex with H-2K(b), and different fates of the thymocytes expressing J15 TCRs in various thymic antigenic environments.

Alleviation of skin inflammation after Lin(-) cell transplantation correlates with their differentiation into myeloid-derived suppressor cells.

To understand the cellular mechanism underlying the therapeutic effects exerted by hematopoietic stem cell transplantation in the repair of tissue damage, we investigated the in vivo dynamics of bone marrow (BM) lineage-negative (Lin(-)) cells transplanted into mice with hyper sensitivity dermatitis. Longitudinal in vivo imaging and flow cytometry analyses revealed that Lin(-) cells home directly to inflamed skin within 6 h, where they undergo extensive expansion with the peak on day 14 post-transplantation, and preferential differentiation into CD11b(+)Ly6G(int)Ly6C(+) cells by day 7. Cells with phenotypic profiles of neutrophils, macrophages, and DCs appeared in inflamed skin on day 14.

Memory programming in CD8(+) T-cell differentiation is intrinsic and is not determined by CD4 help.

CD8(+) T cells activated without CD4(+) T-cell help are impaired in memory expansion. To understand the underlying cellular mechanism, here we track the dynamics of helper-deficient CD8(+) T-cell response to a minor histocompatibility antigen by phenotypic and in vivo imaging analyses. Helper-deficient CD8(+) T cells show reduced burst expansion, rapid peripheral egress, delayed antigen clearance and continuous activation, and are eventually exhausted.

Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow.

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients.

The condensin component NCAPG2 regulates microtubule-kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores.

The early event of microtubule-kinetochore attachment is a critical stage for precise chromosome segregation. Here we report that NCAPG2, which is a component of the condensin II complex, mediates chromosome segregation through microtubule-kinetochore attachment by recruiting PLK1 to prometaphase kinetochores. NCAPG2 colocalizes with PLK1 at prometaphase kinetochores and directly interacts with the polo-box domain (PBD) of PLK1 via its highly conserved C-terminal region.

Kinetics of IFN-γ and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease.

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-γ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 → BALB.

Intravesical instillation of c-MYC inhibitor KSI-3716 suppresses orthotopic bladder tumor growth.

Purpose: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts.

Materials And Methods: The small molecule KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an intravesical chemotherapy agent.

Sixteenth century Gymnophalloides seoi infection on the coast of the Korean Peninsula.

Gymnophalloides seoi is a trematode species discovered as recently as 1993. Interestingly, ancient G. seoi eggs were identified in our earlier study on a 17th Century female mummy unearthed in a Korean county (HD-1) where G.