A5012160371- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- vaccines and immunoinformatics approaches
- Renal and related cancers
- Melanoma and MAPK Pathways
- Renal cell carcinoma treatment
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Quinazolinone synthesis and applications
- Virus-based gene therapy research
- HER2/EGFR in Cancer Research
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
National Institutes of Health
2012-2024
National Cancer Institute
2012-2023
Center for Cancer Research
2008-2022
The University of Tokyo
1991-2012
RIKEN
2012
Iwate Medical University
2012
Yamaguchi University
2012
Foundation for Human Potential
2010
Hirosaki University
1997-2008
National Cancer Institute
2008
Hematopoietic stem cells (HSCs) supply all blood throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog CD34 (mCD34) was used purify HSCs near homogeneity. Unlike in humans, primitive adult bone marrow were detected mCD34 low negative fraction. Injection a single mCD34(lo/-), c-Kit+, Sca-1(+), lineage markers (Lin-) cell resulted long-term reconstitution lymphohematopoietic system 21 percent...
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression metastatic melanoma; however, TILs are a heterogeneous population, and there no effective markers to specifically identify select the repertoire tumor-reactive mutation-specific CD8+ lymphocytes. The lack biomarkers limits ability study these cells develop strategies enhance clinical efficacy extend this therapy other malignancies. Here, we evaluated unique phenotypic traits TCR β chain (TCRβ) clonotypic...
Abstract Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) results in complete regression of advanced cancer some patients, but the efficacy this potentially curative may be limited by poor persistence TIL after adoptive transfer. Pharmacologic inhibition serine/threonine kinase Akt has recently been shown to promote immunologic memory virus-specific murine models, whether approach enhances features (e.g., long-term persistence) that are characteristically...
The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures CD8
KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations are single amino acid substitutions at codon 12, particular G12D and G12V present 60% to 70% pancreatic cancers 20% 30% colorectal consistency, frequency, tumor specificity these "neoantigens" make them attractive therapeutic targets. Recent data associate T cells that target antigens with clinical immunotherapy responses patients metastatic melanoma, lung cancer, or...
CD8+ tumor-infiltrating lymphocytes (TILs) in human melanomas express high levels of PD-1 and are functionally impaired. However, adoptive cell therapy using vitro-expanded TIL can be a highly effective for patients with advanced melanoma. This discrepancy led us to further analyze the CD8+PD-1+ TILs. We found that percentage PD-1-expressing T cells was higher tumor digests generate tumor-reactive TILs after vitro culture interleukin-2 (P=0.0007). Also sorted expanded showed much...
Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding immune cells and their target antigens that mediate tumor regression urgently needed develop more effective approaches for Here we report renal carcinoma (RCC) in following nonmyeloablative consistent graft-versus-tumor effect. We...
During the preparation of manuscript, definition error bars was inadvertently omitted.In all figures, indicate SEM.
A variety of unconventional translational and posttranslational mechanisms contribute to the production antigenic peptides, thereby increasing diversity peptide repertoire presented by MHC class I molecules. Here, we describe a I-restricted that combines several modifications. It is derived from tyrosinase recognized tumor-infiltrating lymphocytes isolated melanoma patient. This unusual made two noncontiguous fragments are spliced together in reverse order. In addition, it contains aspartate...
Abstract Purpose: CD70 expression in normal tissues is restricted to activated lymphoid tissues. Targeting on CD70-expressing tumors could mediate “on-target, off-tumor” toxicity. This study was evaluate the feasibility and safety of using anti-human CARs treat cancer patients whose express CD70. Experimental Design: Seven with binding moieties from human CD27 combined CD3-zeta different costimulatory domains CD28 and/or 41BB were constructed. In vitro functionality these receptors compared...
Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding T-cell to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated ability patient-derived organoids (PDTO) fulfill this need evaluated their utility tool for selecting T-cells adoptive therapy. PDTO established from metastases...
It has been suggested that antitumor T cells specifically traffic to the tumor site, where they effect destruction. To test whether tumor-reactive CD8(+) home tumor, we assessed trafficking of gp100-specific pmel-1 large, vascularized tumors express or do not target Ag. Activation tumor-specific with IL-2 and vaccination an altered peptide ligand caused regression gp100-positive (B16), but gp100-negative (methylcholanthrene 205), implanted on opposing flanks same mouse. Surprisingly, found...
Abstract Peptide splicing is a newly described mode of production antigenic peptides presented by MHC class I molecules, whereby two noncontiguous fragments the parental protein are joined together after excision intervening segment. Three spliced have been described. In cases, involved short segment 4 or 6 aa and was shown to occur in proteasome transpeptidation resulting from nucleophilic attack an acyl-enzyme intermediate N terminus other peptide fragment. For third peptide, which derived...
Clear cell renal carcinoma (RCC) is considered an immunogenic tumor, but it has been difficult to identify tumor-infiltrating lymphocytes (TIL) that show in vitro tumor recognition. We compared the characteristics of fresh RCC TIL peripheral blood (PBL) or melanoma TIL. Our results showed contained fewer CD27(+) T cells, and naïve central memory (CM) more effector (EM) cells than PBL. hypothesized factors microenvironment were skewing phenotype toward EM. One possibility was expression CD70...
The gene and protein structure of the mouse UBF (mUBF), a transcription factor for ribosomal RNA gene, have been determined by cDNA genomic clones. unique mUBF consists 21 exons spanning over 13 kb. Two mRNAs coding mUBF1 mUBF2 having 765 a.a. 728 a.a., respectively, are produced an alternative splicing exon 8. It specifies 37 amino acids constituting part regions homologous to high mobility group proteins (HMG box 2). A human (hUBF) obtained polymerase chain reaction also indicates presence...
The adoptive cell transfer (ACT) of T cells targeting mutated neoantigens can cause objective responses in varieties metastatic cancers, but the development new cell-based treatments relies on accurate animal models. To investigate therapeutic effect a neoantigen with ACT, we used from pmel-1 receptor-transgenic mice, known to recognize WT peptide, gp100, and version peptide that has higher avidity. We gene-engineered B16 express or gp100 epitopes found pmel-1-specific tumor target augmented...
Astrocytic tumors frequently express Fas/APO-1 (Fas), in sharp contrast to surrounding normal brain cells, providing a potential window through which selective killing of tumor cells could be pursued. To assess this possibility, we transduced Fas into U251, glioma cell line resistant anti-Fas antibody-mediated apoptosis, and obtained transfectants with high levels expression. Anti-Fas antibody showed significantly enhanced cytotoxicity for the transfectants, suggesting that U251 maintained...
We previously demonstrated that CD82, expressed on both T cells and antigen-presenting (APC), plays an important role as a co-stimulatory molecule especially in the early phase of cell activation. also showed CD82 expression level is up-regulated activated memory cells. This up-regulation enhances cell-T cell-APC interactions. In this study, we further investigated mechanism CD82-mediated cell-cell adhesion. The enhanced adhesion between CD82-overexpressing Jurkat was completely blocked by...