Academisch Ziekenhuis Leiden

Rene Everardus Maria Toes

Cornelis Johannes Maria Melief

Rienk Offringa

Sjoerd Hendrikus Van Der Burg

Annemieke Geluk

Maria Johanna Philomena Schoenmaekers-Welters

Annemieke M De Jong

Tom H M Ottenhoff

Tom H M Ottenhorf

Tom Henricus Maria Ottenhof

The invention is concerned with epitopes derived from human papilloma virus, and peptides having a size of about 22-45 amino acid residues comprising minimal T cell epitopes. The invention further provides clinically relevant approaches for immunizing subjects against (Myco)bacterially and/or virally infected cells or tumor cells, and in particular against HPV. The invention demonstrates that peptide sequences of 22-35 amino acid residues in length can induce both peptide-specific CD8+ cytolytic cells and CD4+ T-helper cells. Moreover, the invention demonstrates that vaccination with 22-35 residue long peptides results in a more vigorous CD8+ cytolytic T-cell response than vaccination with peptides of the exact minimal CTL epitope length. The invention further demonstrates that the intrinsic capacity of certain minimal CTL epitopes which instead of activating cytolytic effector cells tolerize these cytolytic cells, can be overcome by use of these 22-35 amino acid long peptides. The invention further provides clinically relevant approaches for vaccination and/or treatment of subjects against HPV. The invention also provides methods and uses suited to treat subjects suffering from progressive lesions and/or cervical cancer.

Long peptides of 22-45 amino acid residues that induce and/or enhance antigen specific immune responses

The invention is concerned with epitopes derived from human papilloma virus, and peptides having a size of about 22&#x2013;45 amino acid residues comprising minimal T cell epitopes. The invention further provides clinically relevant approaches for immunizing subjects against (Myco)bacterially and/or virally infected cells or tumor cells, and in particular against HPV. The invention demonstrates that peptide sequences of 22&#x2013;35 amino acid residues in length can induce both peptide-specific CD8+ cytolytic cells and CD4+ T-helper cells. Moreover, the invention demonstrates that vaccination with 22&#x2013;35 residue long peptides results in a more vigorous CD8+ cytolytic T-cell response than vaccination with peptides of the exact minimal CTL epitope length. The invention further demonstrates that the intrinsic capacity of certain minimal CTL epitopes which instead of activating cytolytic effector cells tolerize these cytolytic cells, can be overcome by use of these 22&#x2013;35 amino acid long peptides. The invention further provides clinically relevant approaches for vaccination and/or treatment of subjects against HPV. The invention also provides methods and uses suited to treat subjects suffering from progressive lesions and/or cervical cancer.

Growing community of inventors

Leiden, Netherlands

Rene Everardus Maria Toes