A Phase II Study of Active Immunotherapy With GRNVAC1, Autologous Mature Dendritic Cells Transfected With mRNA Encoding Human Telomerase Reverse Transcriptase, in Patients With Acute Myelogenous Leukemia in Complete Clinical Remission

This is a phase II study to evaluate the safety, feasibility and efficacy of immunotherapy with GRNVAC1 in patients with AML.

Start Date01 Jul 2007

Sponsor / Collaborator

Asterias Biotherapeutics, Inc.

100 Clinical Results associated with TERT x LAMP-1

100 Translational Medicine associated with TERT x LAMP-1

0 Patents (Medical) associated with TERT x LAMP-1

Literatures (Medical) associated with TERT x LAMP-1

27 Aug 2020·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

Entry of Epidemic Keratoconjunctivitis-Associated Human Adenovirus Type 37 in Human Corneal Epithelial Cells

Q2 · MEDICINE

ArticleOA

Author: Chodosh, James ; Mukherjee, Santanu ; Lee, Ji Sun ; Rajaiya, Jaya ; Lee, Jeong Yoon ; Saha, Amrita ; Painter, David F.

PurposeOcular infection by human adenovirus species D type 37 (HAdV-D37) causes epidemic keratoconjunctivitis, a severe, hyperacute condition. The corneal component of epidemic keratoconjunctivitis begins upon infection of corneal epithelium, and the mechanism of viral entry dictates subsequent proinflammatory gene expression. Therefore, it is important to understand the specific pathways of adenoviral entry in these cells.MethodsTransmission electron microscopy of primary and tert-immortalized human corneal epithelial cells infected with HAdV-D37 was performed to identify the means of viral entry. Confocal microscopy was used to determine intracellular trafficking. The results of targeted small interfering RNA and specific chemical inhibitors were analyzed by quantitative PCR, and Western blot.ResultsBy transmission electron microscopy, HAdV-D37 was seen to enter by both clathrin-coated pits and macropinocytosis; however, entry was both pH and dynamin 2 independent. Small interfering RNA against clathrin, AP2A1, and lysosome-associated membrane protein 1, but not early endosome antigen 1, decreased early viral gene expression. Ethyl-isopropyl amiloride, which blocks micropinocytosis, did not affect HAdV-D37 entry, but IPA, an inhibitor of p21-activated kinase, and important to actin polymerization, decreased viral entry in a dose-dependent manner.ConclusionsHAdV-D37 enters human corneal epithelial cells by a noncanonical clathrin-mediated pathway involving lysosome-associated membrane protein 1 and PAK1, independent of pH, dynamin, and early endosome antigen 1. We showed earlier that HAdV-D37 enters human keratocytes through caveolae. Therefore, epidemic keratoconjunctivitis-associated viruses enter different corneal cell types via disparate pathways, which could account for a relative paucity of proinflammatory gene expression upon infection of corneal epithelial cells compared with keratocytes, as seen in prior studies.

01 Sep 2013·Cancer Immunology ResearchQ1 · MEDICINE

Highly Optimized DNA Vaccine Targeting Human Telomerase Reverse Transcriptase Stimulates Potent Antitumor Immunity

Q1 · MEDICINE

Article

Author: Khan, Amir S. ; Morrow, Matthew P. ; Yan, Jian ; Weiner, David B. ; Walters, Jewell N. ; Obeng-Adjei, Nyamekye ; Sardesai, Niranjan Y. ; Shin, Thomas H. ; Pankhong, Panyupa

AbstractHigh levels of human telomerase reverse transcriptase (hTERT) are detected in more than 85% of human cancers. Immunologic analysis supports that hTERT is a widely applicable target recognized by T cells and can be potentially studied as a broad cancer immunotherapeutic, or a unique line of defense against tumor recurrence. There remains an urgent need to develop more potent hTERT vaccines. Here, a synthetic highly optimized full-length hTERT DNA vaccine (phTERT) was designed and the induced immunity was examined in mice and non-human primates (NHP). When delivered by electroporation, phTERT elicited strong, broad hTERT-specific CD8 T-cell responses including induction of T cells expressing CD107a, IFN-γ, and TNF-α in mice. The ability of phTERT to overcome tolerance was evaluated in an NHP model, whose TERT is 96% homologous to that of hTERT. Immunized monkeys exhibited robust [average 1,834 spot forming unit (SFU)/106 peripheral blood mononuclear cells (PBMC)], diverse (multiple immunodominant epitopes) IFN-γ responses and antigen-specific perforin release (average 332 SFU/106 PBMCs), suggesting that phTERT breaks tolerance and induces potent cytotoxic responses in this human-relevant model. Moreover, in an HPV16-associated tumor model, vaccination of phTERT slows tumor growth and improves survival rate in both prophylactic and therapeutic studies. Finally, in vivo cytotoxicity assay confirmed that phTERT-induced CD8 T cells exhibited specific cytotoxic T lymphocyte (CTL) activity, capable of eliminating hTERT-pulsed target cells. These findings support that this synthetic electroporation-delivered DNA phTERT may have a role as a broad therapeutic cancer vaccine candidate. Cancer Immunol Res; 1(3); 179–89. ©2013 AACR.

15 Mar 2005·The Journal of ImmunologyQ2 · MEDICINE

Telomerase mRNA-Transfected Dendritic Cells Stimulate Antigen-Specific CD8+ and CD4+ T Cell Responses in Patients with Metastatic Prostate Cancer

Q2 · MEDICINE

Article

Author: Sichi, Sylvia ; Su, Zhen ; Vieweg, Johannes ; Yancey, Donna ; Coleman, Doris ; Gilboa, Eli ; Dannull, Jens ; Dahm, Philipp ; Yang, Benjamin K. ; Boczkowski, David ; Niedzwiecki, Donna

AbstractTelomerase reverse transcriptase (hTERT) represents an attractive target for cancer immunotherapy because hTERT is reactivated in most human tumors. A clinical trial was initiated in which hTERT mRNA-transfected dendritic cells (DC) were administered to 20 patients with metastatic prostate cancer. Nine of these subjects received DC transfected with mRNA encoding a chimeric lysosome-associated membrane protein-1 (LAMP) hTERT protein, allowing for concomitant induction of hTERT-specific CD8+ and CD4+ T cell responses. Treatment was well tolerated. Intense infiltrates of hTERT-specific T cells were noted at intradermal injection sites after repeated vaccination. In 19 of 20 subjects, expansion of hTERT-specific CD8+ T cells was measured in the peripheral blood of study subjects, with 0.9–1.8% of CD8+ T cells exhibiting Ag specificity. Patients immunized with the chimeric LAMP hTERT vaccine developed significantly higher frequencies of hTERT-specific CD4+ T cells than subjects receiving DC transfected with the unmodified hTERT template. Moreover, CTL-mediated killing of hTERT targets was enhanced in the LAMP hTERT group, suggesting that an improved CD4+ response could augment a CTL response. Vaccination was further associated with a reduction of prostate-specific Ag velocity and molecular clearance of circulating micrometastases. Our findings provide a rationale for further development of hTERT-transfected DC vaccines in the treatment of prostate and other cancers.

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