Institut National De La Sante Et De La Recherche Medicale

Institut Gustave Roussy

Institut Pasteur

Kostas Kosmatopoulos

Sophie Tourdot

Antonio Scardino

Pierre Langlade-Demoyen

Sylvain Cardinaud

Jeanne Menez-Jamet

Fransisco Garcia Pons

Olivier Adotevi

Christine Neuveut

Stéphanie Graff-Dubois

David Alexandre Gross

Alexandre David Gross

This invention relates to the field of anticancer therapy, and to the identification of immunogenic peptides derived from the human telomerase reverse transcriptase (hTERT). The present invention relates to polynucleotides encoding hTERT epitopes restricted to MHC class I molecule, analogues thereof and polyepitopes containing such epitopes and/or analogues. Are also included in the present invention, vector and cell comprising such polynucleotides. The present invention also concerns composition comprising hTERT polypeptides, corresponding polynucleotides, vectors and cells, for use in the treatment and/or prevention of cancer.

Polynucleotides encoding MHC class I-restricted hTERT epitopes, analogues thereof or polyepitopes

Identifying subdominant/cryptic epitopes (I) that are presented by a HLA (human leukocyte antigen) Class I molecule, is new. Identifying subdominant/cryptic epitopes (I) that are presented by a HLA (human leukocyte antigen) Class I molecule comprising selecting at least one peptide (II) of 8-11 amino acids (aa), potentially representing an epitope for Class I presentation, from a protein against which a cytotoxic T cell (CTL) response is to be raised. (II) corresponds to a non-immunogenic peptide with low affinity for Class I molecules. Variants (IIa) of (II) are prepared in which the N-terminal aa is replaced by Tyr and their immunogenicity detected by identifying those that generate a CTL response against target cells expressing the parent protein. Peptide sequences from which active (IIa) are derived are then identified. Independent claims are also included for the following: (1) immunogenic peptide epitopes (IIa) derived from (I) identified this way; and (2) nucleic acid (III) that encodes chimeric polypeptides (IV) containing one or more, same or different, copies of (IIa).

Method for screening peptides for use in immunotherapy

The invention relates to the production of peptide epitopes common to a plurality of antigens of the same multigene family, said epitopes containing at least one common pentapeptide sequence preceded by three amino acids at the N-terminal end and optionally followed by one or two amino acids at the C-terminal end. The invention also relates to polynucleotides coding for said epitopes. Said peptides and polynucleotides can be especially used in anti-tumour immunotherapy.

Peptide epitopes common to antigens of the same multigene family

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Paris, France

Kostas Kosmatopoulos