scholarly journals Immunotherapy-induced antibodies to endogenous retroviral envelope glycoprotein confer tumor protection in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248903
Author(s):  
Byong H. Kang ◽  
Noor Momin ◽  
Kelly D. Moynihan ◽  
Murillo Silva ◽  
Yingzhong Li ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Tumor Antigens ◽  
Humoral Response ◽  
Endogenous Retrovirus ◽  
B16f10 Cells ◽  
Tumor Protection ◽  
Prophylactic Vaccination ◽  
Allogeneic Tumor Cell ◽  
Env Protein ◽  
Subcutaneous Inoculation

Following curative immunotherapy of B16F10 tumors, ~60% of mice develop a strong antibody response against cell-surface tumor antigens. Their antisera confer prophylactic protection against intravenous challenge with B16F10 cells, and also cross-react with syngeneic and allogeneic tumor cell lines MC38, EL.4, 4T1, and CT26. We identified the envelope glycoprotein (env) of a murine endogenous retrovirus (ERV) as the antigen accounting for the majority of this humoral response. A systemically administered anti-env monoclonal antibody cloned from such a response protects against tumor challenge, and prophylactic vaccination against the env protein protects a majority of naive mice from tumor establishment following subcutaneous inoculation with B16F10 cells. These results suggest the potential for effective prophylactic vaccination against analogous HERV-K env expressed in numerous human cancers.

scholarly journals Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3408
Author(s):  
Karita Peltonen ◽  
Sara Feola ◽  
Husen M. Umer ◽  
Jacopo Chiaro ◽  
Georgios Mermelekas ◽  
...  
Keyword(s):  
Tumor Antigens ◽  
Endogenous Retrovirus ◽  
Peptide Ligands ◽  
Tumor Control ◽  
Preclinical Model ◽  
Vaccine Platform ◽  
Therapeutic Cancer Vaccine ◽  
Mhc I ◽  
Specific Tumor ◽  
Therapeutic Cancer Vaccines

Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interrogating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexible and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating immunopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.

scholarly journals Envelope Gene of the Human Endogenous Retrovirus HERV-W Encodes a Functional Retrovirus Envelope

2001 ◽  
Vol 75 (7) ◽  
pp. 3488-3489 ◽  
Author(s):  
Dong Sung An ◽  
Yi-ming Xie ◽  
Irvin S. Y. Chen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Functional Properties ◽  
Envelope Glycoprotein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Envelope Gene ◽  
Membrane Glycoprotein ◽  
Herv Family ◽  
Immunodeficiency Virus

ABSTRACT A member of the human endogenous retrovirus (HERV) family termed HERV-W encodes a highly fusogenic membrane glycoprotein that appears to be expressed specifically in the placenta. It is unclear whether the glycoproteins of the HERVs can serve as functional retrovirus envelope proteins to confer infectivity on retrovirus particles. We found that the HERV-W envelope glycoprotein can form pseudotypes with human immunodeficiency virus type 1 virions and confers tropism for CD4-negative cells. Thus, the HERV-W env gene represents the first HERV env gene demonstrated to encode the functional properties of a retrovirus envelope glycoprotein.

Increased humoral and cellular immunity in patients (pts) with advanced melanoma treated with ipilimumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3031-3031
Author(s):  
S. Parker ◽  
D. Berman ◽  
K. L. Bennett ◽  
S. Alaparthy ◽  
Z. Tsuchihashi ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Immunity ◽  
Tumor Antigens ◽  
Humoral Response ◽  
Skin Tests ◽  
Clinical Activity ◽  
Dependent Manner ◽  
Tumor Vaccines ◽  
Maximum Increase ◽  
Hla Dr

3031 Background: Ipilimumab is an anti-CTLA-4 monoclonal antibody (Ab) that overcomes T-cell suppression. In this phase II study (CA184004), humoral and cellular responses were assessed in ipilimumab-treated pts with unresectable stage III/IV melanoma. Methods: Ipilimumab 3 or 10 mg/kg was given every 3 weeks x 4. Tetanus boosters were given ≤10 days pre-treatment. Influenza and pneumococcal vaccines were given 5 days after first ipilimumab dose. Tetanus, anti-influenza, and anti-pneumococcal Ab levels were assessed at pre-dose and Wk 7. Humoral response to 5 tumor antigens (Ag) and a control Ag (DHFR) were examined at baseline (BL) and at Wks 4, 8–9, and 12. DTH skin tests were given at pre-dose and Wk 4, with responses recorded 15 minutes (min) and 24–72 hours (hrs) post-test. Peripheral T-cell populations were evaluated through flow cytometry at BL, Wk 4, and Wk 12. Results: Pts received ipilimumab 3 (n = 40) or 10 mg/kg (n = 42). Increases from BL in humoral responses to pneumococcal (40–50/78 pts, depending on Ab) and tetanus (58/78 pts) vaccines were noted, even in pts who did not receive on-study pneumococcal (4–9 pts) or tetanus (7 pts) vaccines. Increased humoral response to influenza only occurred in pts receiving the influenza vaccine. Maximum increase from BL of ≥ 5-fold titer (clinically meaningful threshold) in humoral response to tumor Ag MELANA (23.2% of pts), SSX2 (20.3%), NYES01 (18.8%), MAGEA4 (10.1%), and P53 (4.3%) (DHFR, 4.3%) was noted without tumor vaccines. Tumor Ag response was not associated with clinical activity (complete or partial response, or stable disease ≥ 24 wks). Increased DTH reactions were noted for tetanus, 24–72 hrs (3 mg/kg: 5/7 pts; 10 mg/kg: 3/6 pts); tuberculin, 15 min (3 mg/kg: 7/15 pts; 10 mg/kg: 4/15 pts); Candida, 15 min (3 mg/kg: 4/6 pts; 10 mg/kg: 2/7 pts); and Trichophyton, 15 min (3 mg/kg: 3/4 pts; 10 mg/kg: 2/5 pts). Significant increases from BL in percents of HLA-DR+ CD4+ (p = 9.3x10-7), HLA-DR+ CD8+ (p = 0.018), and ICOS+ CD4+ (p = 0.0027) effector T cells were noted. Conclusions: Humoral immunity in ipilimumab-treated pts increased (± vaccination) in an Ag-dependent manner and cellular immunity was enhanced. Change in tumor Ag response was not associated with clinical activity. [Table: see text]

scholarly journals An Envelope Glycoprotein of the Human Endogenous Retrovirus HERV-W Is Expressed in the Human Placenta and Fuses Cells Expressing the Type D Mammalian Retrovirus Receptor

2000 ◽  
Vol 74 (7) ◽  
pp. 3321-3329 ◽  
Author(s):  
Jean-Luc Blond ◽  
Dimitri Lavillette ◽  
Valérie Cheynet ◽  
Olivier Bouton ◽  
Guy Oriol ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Expression Vector ◽  
Physiological Role ◽  
Endogenous Retrovirus ◽  
Open Reading Frame ◽  
Human Endogenous Retrovirus ◽  
Membrane Glycoprotein ◽  
Reading Frame ◽  
Herv Family ◽  
Type D

ABSTRACT A new human endogenous retrovirus (HERV) family, termed HERV-W, was recently described (J.-L. Blond, F. Besème, L. Duret, O. Bouton, F. Bedin, H. Perron, B. Mandrand, and F. Mallet, J. Virol. 73:1175–1185, 1999). HERV-W mRNAs were found to be specifically expressed in placenta cells, and an env cDNA containing a complete open reading frame was recovered. In cell-cell fusion assays, we demonstrate here that the product of the HERV-W env gene is a highly fusogenic membrane glycoprotein. Transfection of an HERV-W Env expression vector in a panel of cell lines derived from different species resulted in formation of syncytia in primate and pig cells upon interaction with the type D mammalian retrovirus receptor. Moreover, envelope glycoproteins encoded by HERV-W were specifically detected in placenta cells, suggesting that they may play a physiological role during pregnancy and placenta formation.

scholarly journals SARS-CoV-2 induces transcription of human endogenous retrovirus RNA followed by type W envelope protein expression in human lymphoid cells.

2021 ◽  
Author(s):  
Benjamin Charvet ◽  
Magalie Mazelier ◽  
Joanna Brunel ◽  
Justine Pierquin ◽  
Said Mougari ◽  
...  
Keyword(s):  
Protein Expression ◽  
Viral Infections ◽  
Endogenous Retrovirus ◽  
Lymphoid Cells ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Initial Exposure ◽  
Pbmc Culture ◽  
Healthy Donors ◽  
Env Protein

Abstract Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after resolution of the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. We demonstrate here that an initial exposure to SARS-CoV-2 virus activates early HERV-W and K transcription in peripheral blood mononuclear cell (PBMC) cultures from healthy donors. Within a week of primary PBMC culture, only HERV-W ENV protein expression was detected in lymphoid cells of some donors, although SARS-CoV-2 infection of PBMC was not observed. HERV activation was reproduced with UV-inactivated virus and with a recombinant spike protein. Interestingly, exposure to SARS-CoV-2 protein induced a significant production of interleukin 6 in PBMC, independently from detectable HERV expression. Altogether, these results show that SARS-CoV-2 viral protein could induce HERV-W ENV expression in lymphocytes from some individuals, underlying the importance to further address the implicated molecular pathways, to understand patients‘ genetic susceptibility associated to the activation of HERV-W and its possible relevance for targeting therapeutic intervention in COVID-19 associated syndromes.

Autoantibodies against unmodified and citrullinated human endogenous retrovirus K envelope protein in rheumatoid arthritis patients

2021 ◽  
pp. jrheum.201492
Author(s):  
Xiaoxing Wang ◽  
Amanda Hefton ◽  
Kathryn Ni ◽  
Kennedy C. Ukadike ◽  
Michael A. Bowen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Adult ◽  
Endogenous Retrovirus ◽  
Arginine Deiminase ◽  
Human Endogenous Retrovirus ◽  
Published Data ◽  
Erosive Disease ◽  
Protein Arginine Deiminase ◽  
Env Protein ◽  
Neutrophil Cell

Objective Autoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K. Methods Immunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase (PAD) 4. Sera from 100 RA patients, plasma from 32 juvenile idiopathic arthritis (JIA) patients, and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory parameters of the patients. Results We replicated and expanded upon published data that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating DNA-myeloperoxidase complexes indicative of nonapoptotic neutrophil cell death. Furthermore, most of the RA patients, but not JIA patients, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease. Conclusion Our data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.

scholarly journals Proteomic-Based Approach for the Identification of Tumor Markers Associated with Hepatocellular Carcinoma

2001 ◽  
Vol 17 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Philip Shalhoub ◽  
Sarah Kern ◽  
Sophie Girard ◽  
Laura Beretta
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Antigens ◽  
Humoral Response ◽  
Mass Spectrometry Analysis ◽  
Major Type ◽  
Two Dimensional Gel Electrophoresis ◽  
Spectrometry Analysis ◽  
Immune Response To Cancer ◽  
Specific Proteins ◽  
The Common

There is increasing evidence for an immune response to cancer in humans, demonstrated in part by the identification of autoantibodies to tumor antigens. The identification of panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis or in establishing prognosis. Several approaches are currently available for the identification of tumor antigens. We have used a proteomic-based approach for the identification of tumor antigens that induce an antibody response which we have applied to hepatocellular carcinoma, a major type of cancer worldwide. Two-dimensional gel electrophoresis allows simultaneous separation of several thousand individual proteins from tumor tissue or tumor cell lines. Proteins eliciting a humoral response in HCC were identified by 2-D Western blotting using sera from patients with hepatocellular carcinoma, followed by mass spectrometry analysis and database search. The common occurrence of autoantibodies to specific proteins may have utility for HCC screening and diagnosis.

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