scholarly journals Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells

2006 ◽  
Author(s):  
Yoshiyuki Yamaguchi ◽  
Akiko Ohshita ◽  
Katsuji Hironaka ◽  
Riki Okita ◽  
Makoto Okawaki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Adoptive Immunotherapy ◽  
Hla Class I ◽  
Class I ◽  
Allogeneic Tumor

The Effects of Epigenetic Modifiers on PD‐L1 and HLA Class I Expression on Tumor Cells

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Trisha Maini ◽  
Lauren Sternberg ◽  
Robert W. O'Donnell
Keyword(s):  
Tumor Cells ◽  
Hla Class I ◽  
Class I ◽  
Epigenetic Modifiers

scholarly journals Preclinical characterization of 1-7F9, a novel human anti–KIR receptor therapeutic antibody that augments natural killer–mediated killing of tumor cells

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2667-2677 ◽  
Author(s):  
Francois Romagné ◽  
Pascale André ◽  
Pieter Spee ◽  
Stefan Zahn ◽  
Nicolas Anfossi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Hla Class I ◽  
Therapeutic Antibody ◽  
Class I ◽  
Therapeutic Window ◽  
Target Cells ◽  
Term Survival

Abstract Inhibitory-cell killer immunoglobulin-like receptors (KIR) negatively regulate natural killer (NK) cell–mediated killing of HLA class I–expressing tumors. Lack of KIR-HLA class I interactions has been associated with potent NK-mediated antitumor efficacy and increased survival in acute myeloid leukemia (AML) patients upon haploidentical stem cell transplantation from KIR-mismatched donors. To exploit this pathway pharmacologically, we generated a fully human monoclonal antibody, 1-7F9, which cross-reacts with KIR2DL1, -2, and -3 receptors, and prevents their inhibitory signaling. The 1-7F9 monoclonal antibody augmented NK cell–mediated lysis of HLA-C–expressing tumor cells, including autologous AML blasts, but did not induce killing of normal peripheral blood mononuclear cells, suggesting a therapeutic window for preferential enhancement of NK-cell cytotoxicity against malignant target cells. Administration of 1-7F9 to KIR2DL3-transgenic mice resulted in dose-dependent rejection of HLA-Cw3–positive target cells. In an immunodeficient mouse model in which inoculation of human NK cells alone was unable to protect against lethal, autologous AML, preadministration of 1-7F9 resulted in long-term survival. These data show that 1-7F9 confers specific, stable blockade of KIR, boosting NK-mediated killing of HLA-matched AML blasts in vitro and in vivo, providing a preclinical basis for initiating phase 1 clinical trials with this candidate therapeutic antibody.

Mechanisms of loss of HLA class I expression on colorectal tumor cells

1996 ◽  
Vol 47 (5) ◽  
pp. 364-371 ◽  
Author(s):  
M. Browning ◽  
F. Petronzelli ◽  
D. Bicknell ◽  
P. Krausa ◽  
A. Rowan ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hla Class I ◽  
Colorectal Tumor ◽  
Class I

HLA Class I and EBV Positive Classical Hodgkin Lymphoma In the Chinese Population

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2688-2688
Author(s):  
Huang Xin ◽  
Arjan Diepstra ◽  
Zifen Gao ◽  
Lydia Visser ◽  
Hans Vos ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Chinese Population ◽  
Conflicts Of Interest ◽  
Inverse Correlation ◽  
Hla Class I ◽  
Class I ◽  
Antigenic Peptides ◽  
Hla Association ◽  
Barr Virus ◽  
Increased Risk

Abstract Abstract 2688 In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. Since HRS cells also express other components of the antigen presenting pathway it can be anticipated that HRS cells in EBV-positive cHL should be able to present EBV derived antigenic peptides. In on our previous genotyping study we demonstrated that the HLA-A*02 allele was associated with a reduced and the HLA-A*01 allele with an increased risk of developing EBV-positive cHL. Intuitively, this can be explained by the generally acknowledged lack of HLA-A*01 restricted immune responses to latent EBV peptides. In this study, we analyzed HLA class I expression and the HLA association in relation to EBV in Asian cHL patients. Formalin-fixed and paraffin embedded (FFPE) tissue blocks were available for 145 cHL patients and from 79 controls from 5 hospitals from the Northern part of China. Hematoxylin & Eosin-stained sections were used to reclassify the histological subtypes according to the WHO classification. EBV status was determined by EBER in situ hybridization. Membranous expression of HLA class I was detected by immunohistochemistry using antibodies against HLA class I (HC-10) and ß2-microglobulin. DNA was isolated from FFPE samples to detect the HLA-A*02 allele by quantitative PCR. 23 cHL cases and 5 controls were excluded due to poor DNA quality. Positive EBV status was observed in 40% (58/145) of the Chinese cHL patients. As expected, the percentage of EBV-positive cases was much higher in the mixed cellularity subtype (71%) than in the nodular sclerosis subtype (16%; p<0.001). Expression of HLA class I was observed in 79% of the EBV-positive cHL patients and in 30% of the EBV-negative patients (p<0.001) consistent with the previous findings in the Dutch population. The HLA-A*02 allele was detected in 71% of the EBV-positive cHL and in 64% of the EBV-negative cHL patients (NS). In the controls HLA-A*02 was observed in 67% of the cases. In this Chinese population, the tumor cells of EBV-positive cHL more frequently retained membranous HLA class I expression, similar to the Caucasian populations. The inverse correlation between presence of the HLA-A*02 allele and positive EBV status, as observed in Caucasians, is not present in these northern Chinese cHL patients. Differences in ethnic background might explain discrepancies in HLA-A association with EBV-positive cHL in different populations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of HLA Class I and HLA Class II by Tumor Cells in Chinese Classical Hodgkin Lymphoma Patients

PLoS ONE ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. e10865 ◽  
Author(s):  
Xin Huang ◽  
Anke van den Berg ◽  
Zifen Gao ◽  
Lydia Visser ◽  
Ilja Nolte ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class I ◽  
Classical Hodgkin Lymphoma

scholarly journals Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody Nimotuzumab

2017 ◽  
Vol 8 ◽  
Author(s):  
Greta Garrido ◽  
Ailem Rabasa ◽  
Cristina Garrido ◽  
Lisset Chao ◽  
Federico Garrido ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hla Class I ◽  
Class I ◽  
Egfr Antibody

Co-Administration Of Gene-Modified CD4+ T Cells Targeting HLA Class I-Restricted WT1 Epitope Diversely Enhances The Antitumor Effect Mediated By Redirected T-Cell Based Adoptive Immunotherapy Against Human Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 144-144
Author(s):  
Hiroshi Fujiwara ◽  
Fumihiro Ochi ◽  
Toshiki Ochi ◽  
Hiroaki Asai ◽  
Yukihiro Miyazaki ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mouse Model ◽  
Cd8 T Cells ◽  
Adoptive Immunotherapy ◽  
Cd4 T Cells ◽  
Hla Class I ◽  
Class I ◽  
Leukemia Cells

Abstract Purpose In the context of redirected T-cell based antitumor adoptive immunotherapy, the therapeutic roles played by co-infused CD4+ T cells genetically redirected to the predefined HLA class I-restricted epitope which had been originally recognized by effector CD8+ T cells has not yet been fully discussed. In this study, using an HLA class I-restricted WT1 -specific T-cell receptor (TCR) gene transfer, we in detail examined antileukemia functionality mediated by these gene-modified CD4+ T cells co-infused with similarly gene-modified effector CD8+ T cells as the redirected T cell-based adoptive immunotherapy. Methods Using our unique retroviral vector expressing HLA-A*2402-restricted and WT1235-243-specific TCR a/b genes and shRNAs for endogenous TCRs (WT1-siTCR vector), we genetically modified both CD4+ and CD8+ T cells from the same healthy donor or leukemia patients (termed WT1-siTCR/CD4 and WT1-siTCR/CD8, respectively). First, target-responsive cellular outputs mediated by WT1-siTCR/CD4 was thoroughly examined using flowcytometry, ELISA, 51Cr-release assay, CFSE dilution assay and bioluminescence assay. Next we similarly assessed impacts of WT1-siTCR/CD4 on the antileukemia functionality mediated by concurrentWT1-siTCR/CD8 both in vitro and in vivo. Eventually, we assessed the in vivo therapeutic efficacy of combined administration of WT1-siTCR/CD8 with WT1-siTCR/CD4 using a xenografted mouse model. Results The transcription factor profile demonstrated that WT1-siTCR/CD4 turned a terminal effector, but not regulatory phenotype. Activated WT1-siTCR/CD4 expressed cell-surface CD40L. Target-responsive cytokine production profile of WT1-siTCR/CD4 represented the Th1 helper function in the context of HLA-A*2402. HLA class II molecules expressed by leukemia cells facilitated the recognition of leukemia cells by WT1-siTCR/CD4 in the context of HLA-A*2402. WT1-siTCR/CD4 displayed the delayed cytocidal activity determined by 51Cr release assay. WT1-siTCR/CD4 could produce IFN-g in response to freshly isolated leukemia cells. WT1-siTCR/CD4 displayed the leukemia trafficking activity in vivo. WT1-siTCR/CD4 represented the potential to migrate into bone marrow via CXCR4/CXCL12 axis both in vitro and in vivo. Concurrent WT1-siTCR/CD4 augmented IFN-g production and cytotoxic degranulation mediated by WT1-siTCR/CD8 in response to the cognate epitope via humoral factors. Consequently, the cytocidal activity against autologous leukemia cells mediated by WT1-siTCR/CD8 was augmented in the presence of WT1-siTCR/CD4, both of them generated from normal lymphocytes of the same patient with leukemia in a complete remission. Upon the target recognition, activated WT1-siTCR/CD4 recruited WT1-siTCR/CD8 via CCL3/4-CCR5 axis. Proliferative response and differentiation into central memory T-cell subset mediated by WT1-siTCR/CD8 in response to the cognate epitope and leukemia cells were enhanced in the presence of autologousWT1-siTCR/CD4, but not gene-modified CD4+ T cells (NGM-CD4). CD127 expression on activated WT1-siTCR/CD8 also increased in parallel to this differentiation. Co-infused WT1-siTCR/CD4 augmented the tumor trafficking and persistence of WT1-siTCR/CD8 in vivo, resulting in the greater suppression of leukemia cells in a xenografted mouse model. Finally, in the therapeutic mouse model, co-infusion of WT1-siTCR/CD8 with of WT1-siTCR/CD4 significantly suppressed the growth of inoculated leukemia cells compared to that in mice received co-infusion of WT1-siTCR/CD8 with NGM-CD4 (Fig.1). Correlation between the therapeutic efficacy and survival of infused gene-modified T cells was also observed. Conclusion In results, the combined infusion of WT1-siTCR/CD8 with WT1-siTCR/CD4, but not NGM-CD4 obviously demonstrates the enhanced antileukemia efficacy via diverse mechanisms. Now we have just started a clinical trial using gene-modified T cells with WT1-siTCR vector for the treatment of patients with refractory acute myeloid leukemia and myeloid dysplastic syndrome. Because redirected T cells employed in this trial encompassed both WT1-siTCR/CD4 and WT1-siTCR/CD8, we are planning to clinically verify the significance of WT1-siTCR/CD4 in the redirected T cell-based antileukemia adoptive immunotherapy. (Fig.1) Disclosures: No relevant conflicts of interest to declare.

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