HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial

2014 ◽  
Vol 66 (5) ◽  
pp. 299-310 ◽  
Author(s):  
Heather A. Prentice ◽  
Philip K. Ehrenberg ◽  
Karen M. Baldwin ◽  
Aviva Geretz ◽  
Charla Andrews ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hla Class I ◽  
Hiv Vaccine ◽  
Class I ◽  
Phase 3 ◽  
Vaccine Clinical Trial ◽  
Genome Wide

Induction of Survivin-Specific, HLA-A24 Restricted Cytotoxic T Lymphocytes Using an Immunodominant Peptide; In-Vitro Feasibility Study and a Clinical Trial of Survivin Peptide Vaccination.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2709-2709
Author(s):  
Masahiro Ogasawara ◽  
Misato Kikuchi ◽  
Satoru Kimura ◽  
Koichiro Kobayashi ◽  
Takayoshi Miyazono ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Lymphocytes ◽  
Healthy Volunteers ◽  
Cytotoxic T Lymphocytes ◽  
Feasibility Study ◽  
Hla Class I ◽  
Class I ◽  
Peptide Vaccination ◽  
Lymphoma Cells

Abstract Survivin, a member of the inhibitors of the apoptosis family, is overexpressed frequently in a variety of cancers and hematological malignancies, but not in normal tissues. Murine in vivo and human in vitro studies have suggested that immunotherapy of cancer patients using survivin peptide might be feasible. In the present study, we examined whether HLA-A24 restricted cytotoxic T lymphocytes (CTL) which recognize survivin peptide can be generated from peripheral blood of lymphoma patients. HLA-A24 positive four lymphoma patients and two healthy volunteers were enrolled. Three immunodominant 9-mer candidate peptides (2B, 3A, 3B) were selected on the basis of anchoring motif of peptide binding to HLA-A24 molecule. CD8 T cells from the patients and healthy volunteers were stimulated several times with autologous monocyte-derived dendritic cells pulsed with survivin or control HIV peptides and tested for peptide-specific cytotoxicity by an LDH-release assay. CTL generated with survivin 2B peptide lysed autologous monocytes pulsed with a relevant peptide. However, other survivin peptides did not elicit CTL response. Non-pulsed or HIV peptide-pulsed monocytes were not lysed. On the other hand, CTL generated with HIV peptide only lysed HIV peptide-pulsed monocytes. CTL did not lyse allogeneic monocytes regardless of the peptide pulse. Cytotoxic activity was inhibited by the pretreatment of target cells by anti-HLA class I, not by anti-HLA-DR monoclonal antibody, indicating that the lysis was HLA class I (A24) restricted. These cells did not lyse Daudi and K562, excluding the involvement of LAK or NK activity. Importantly, these survivin peptide-specific CTL showed cytotoxicity to the patient’s lymphoma cells and HLA-A24 positive lymphoma cells. Based on these preclinical data, we have just started a pilot clinical study to examine the safety and the efficacy of peptide vaccination to relapsed, chemotherapy-resistant malignant lymphoma patients who are HLA-A24 and survivin positive. A 46-year old male patient with diffuse large B-cell lymphoma has just completed two courses of four vaccinations at two-week intervals with survivin 2B peptide (1 μg subcutaneously) in an incomplete Freund’s adjuvant (Montanide ISA-51, SEPPIC Co. France). We observed a marked decrease in the size of extra-nodular surface and cervical lymphnodes following vaccinations without serious adverse events. Immunological evaluations using HLA-tetramer and T cell receptor clonality assays revealed an increase in survivin-specific CTL frequency after vaccinations. The in-vitro feasibility study and pilot clinical trial indicate that a vaccination with a survivin peptide is safe and might be a promising novel strategy for the treatment of lymphoma patients.

Exploring evidence for behavioral risk compensation among participants in an HIV vaccine clinical trial

Vaccine ◽  
2017 ◽  
Vol 35 (28) ◽  
pp. 3558-3563 ◽  
Author(s):  
Julia E. Painter ◽  
Ralph J. DiClemente ◽  
Lauren Jimenez ◽  
Theron Stuart ◽  
Jessica M. Sales ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hiv Vaccine ◽  
Risk Compensation ◽  
Behavioral Risk ◽  
Vaccine Clinical Trial

204 Adolescentsʼ Willingness to Participate in HIV Vaccine Clinical Trial Preparedness in Nigeria

2011 ◽  
Vol 56 ◽  
pp. 87
Author(s):  
N M Otuonye ◽  
I R Onwuatuelo ◽  
J O Okwuzu ◽  
C K Onwuamah ◽  
A K Adeneye ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hiv Vaccine ◽  
Willingness To Participate ◽  
Vaccine Clinical Trial

scholarly journals The SPPL3-defined glycosphingolipid repertoire regulates immune responses by improving HLA class I access

2020 ◽  
Author(s):  
Marlieke L.M. Jongsma ◽  
Matthijs Raaben ◽  
Antonius A. de Waard ◽  
Tao Zhang ◽  
Birol Cabukusta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Patient Survival ◽  
Hla Class I ◽  
Class I ◽  
Potential Therapeutic Target ◽  
Genome Wide ◽  
Approved Drugs

SummaryHLA class I (HLA-I) drives immune responses by presenting antigen-derived peptides to cognate CD8+ T cells. This process is often hijacked by tumors and pathogens for immune evasion. Since therapeutic options for restoring HLA-I antigen presentation are limited, we aimed to identify new HLA-I pathway targets. By iterative genome-wide screens we uncovered that the cell surface glycosphingolipid (GSL) repertoire determines effective HLA-I antigen presentation. We show that absence of the protease SPPL3 augments B3GNT5 enzyme activity, resulting in upregulated levels of surface (neo)lacto-series GSLs. These GSLs sterically impede molecular interactions with HLA-I and diminish CD8+ T cell activation. In accordance, a disturbed SPPL3-B3GNT5 pathway in glioma associates with decreased patient survival. Importantly, we show that this immunomodulatory effect can be reversed through GSL synthesis inhibition using clinically approved drugs. Overall, our study identifies a GSL signature that functionally inhibits antigen presentation and represents a potential therapeutic target in cancer, infection and autoimmunity.

scholarly journals The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

2019 ◽  
Author(s):  
Rebecca L. Yanovsky ◽  
Haoyan Chen ◽  
Stephen Leslie ◽  
Mary Carrington ◽  
Wilson Liao
Keyword(s):  
Genome Wide Association Study ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Antigen Presenting Cells ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
Genome Wide ◽  
Related Group ◽  
Antigen Presenting

ABSTRACTGenetic variation within the major histocompatibility complex (MHC) class I is a well-known risk factor for psoriasis. While the mechanisms behind this variation are still being fully elucidated, human leukocyte antigen (HLA) presentation of auto-antigens as well as the interaction of HLA-B with killer cell immunoglobulin-like receptors (KIRs) have been shown to contribute to psoriasis susceptibility. Here we demonstrate that the interaction of HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR), a related group of immunomodulatory receptors primarily found on antigen presenting cells, also contributes to psoriasis susceptibility. We used previously characterized binding capacities of HLA-A, HLA-B, and HLA-C allotypes to two inhibitory LILRs, LILRB1 and LILRB2, to investigate the effect of LILRB1/2 binding in two large genome wide association study cohorts of psoriasis patients and controls (N = 10,069). We found that the strength of binding of LILRB2 to HLA-B was inversely associated with psoriasis risk (p = 2.34E-09, OR [95% CI], 0.41 [0.30−0.55]) independent of individual class I or II allelic effects. We thus propose that weak binding of inhibitory LILRB2 to HLA-B may play a role in patient susceptibility to psoriasis via increased activity of antigen presenting cells.

scholarly journals Association Between Human Leukocyte Antigen Class I and II Diversity and Non-virus-associated Solid Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiwei Liu ◽  
Allan Hildesheim
Keyword(s):  
Human Leukocyte Antigen ◽  
Solid Tumors ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
European Ancestry ◽  
Leukocyte Antigen ◽  
Genome Wide

Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (Ptrend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors.

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