The Council of the Queensland Institute of Medical Research

Other

Atara Biotherapeutics, Inc.

Rajiv Khanna

Scott Renton Burrows

Dasari Vijayendra

Beverley Mavis Kerr

Denis James Moss

Ihor Stephan Misko

Rebecca Ann Elkington

Susan Jennifer Walker

Corey Smith

Martina Alison Sherritt

Denis James M&ograve;ss

Andreas Suhrbier

Jacqueline Margaret Burrows

Blake Tolu Aftab

An isolated protein comprises respective amino acid sequences of each of a plurality of CTL epitopes from two or more different herpesvirus antigens and further comprises an intervening amino acid or amino acid sequence between at least two of said CTL epitopes comprising proteasome liberation amino acids or amino acid sequences and, optionally, Transporter Associated with Antigen Processing recognition motifs. The isolated protein is capable of rapidly expanding human cytotoxic T lymphocytes (CTL) in vitro and eliciting a CTL immune response in vivo upon administration to an animal as an exogenous protein. Typically, the isolated protein comprises no more than twenty (20) CTL epitopes derived from cytomegalovirus and/or Epstein-Barr virus antigens.

Human herpesvirus immunotherapy

Provided herein are methods and compositions related to the selection T cells and/or subjects for adoptive immunotherapy based on the expression of one or more biomarkers.

Methods of immunotherapy

An isolated protein construct comprising a polyepitope derived from multiple human cytomegalovirus protein antigen epitopes conjugated to an extracellular domain of glycoprotein B, which isolated protein is capable of eliciting a cytotoxic T-lymphocyte immune response as well as a neutralizing antibody response to human cytomegalovirus. Also provided are pharmaceutical compositions comprising the isolated protein or an adenoviral expression construct for delivery and expression of a nucleic acid encoding the isolated protein for prophylactic and/or therapeutic treatment of human cytomegalovirus infection, particularly in humans.

Human cytomegalovirus immunotherapy

The present invention provides CTL epitope peptides and polyepitope peptides from 14 distinct antigens of human cytomegalovirus (HCMV) that are restricted through HLA the most commonly prevalent class I alleles in different ethnic populations of the world. These epitopes provide an important platform for CTL epitope-based vaccines against HCMV. The present invention further provides vaccine compositions comprising the subject epitope and polyepitope peptides and methods for vaccination of humans and for the adoptive transfer of HCMV-specific T cells to human subjects. The present invention further provides reagents and methods for determining the HCMV status or level of HCMV-specific immunity of a subject.

Human cytomegalovirus (HCMV) cytotoxic T cell epitopes, polyepitopes compositions comprising same and diagnostic and prophylactic and therapeutic uses therefor

The present invention provides cytotoxic Epstein-Barr virus (EBV) T-cell epitopes derived from EBV structural antigens. Preferred epitopes include YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ ID NO:8), ILLIIALYL (SEQ ID NO:9), VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID NO:27) and QLTPHTKAV (SEQ ID NO:29). The present invention also provides methods of treating or preventing EBV infection in subjects which involve administration of EBV cytotoxic T-cell epitopes.

CTL epitopes from EBV

The present invention provides cytotoxic Epstein-Barr virus T-cell epitopes. These epitopes are QVKWRMTTL, VFSDGRVAC, VPAPAGPIV, TYSAGIVQI, LLDFVRFMGV, QNGALAINTF, VSSDGRVAC, VSSEGRVAC, VSSDGRVPC, VSSDGLVAC, VSSDGQVAC, VSSDGRVVC, VPAPPVGPIV, VEITPYEPTG, VEITPYEPTW, VELTPYKPTW, RRIYDLIKL, RKIYDLIEL and PYLFWLAGI. The present invention further provides vaccines including one or more of these epitopes, optionally with additional epitopes.

EBV CTL epitopes

The present invention provides an isolated cytotoxic Epstein-Barr virus T-cell epitope having the amino acid sequence TYSAGIVQI (SEQ ID NO: 34) which can be formulated as a water-in-oil formulation, and vaccine compositions comprising said epitope, optionally with additional epitopes.

Growing community of inventors

Herston, Australia

Rajiv Khanna