Academisch Ziekenhuis Leiden

Keygene N.v.

Academisch Ziekenhuis Leiden (h.o.d.n. Lumc)

Leiden University Medical Center

Leids Universitair Medisch Centrum

Rienk Offringa

Cornelis Johannes Maria Melief

Annemieke Geluk

Annemieke M De Jong

Sjoerd Hendrikus Van Der Burg

Maria Johanna Philomena Schoenmaekers-Welters

Tom H M Ottenhoff

Reinaldus Everardus Maria Toes

Rene Everardus Maria Toes

Sjoerd Henricus Van Der Burg

Gemma G Kenter

René Toes

Stephen P Schoenberger

Tom H M Ottenhorf

Sjoerd Hendricus Van Der Burg

Theodorus Jozef Maria Helmerhorst

Cornelis J M Melief

Delphine Gabrielle Josette Rea

Tom Henricus Maria Ottenhof

Sjoerd Henricus Postzone K1-P Van Der Burg

Epitopes derived from human papilloma virus and peptides having a size of about 22-45 amino acid residues comprising minimal T cell epitopes are disclosed. Also disclosed are clinically relevant approaches for immunizing subjects against (Myco) bacterially and/or virally infected cells or tumor cells. Peptide sequences of 22-35 amino acid residues in length can induce both peptide-specific CD8+ cytolytic cells and CD4+ T-helper cells. Moreover, 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 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. Also disclosed are clinically relevant approaches for vaccination and/or treatment of subjects against HPV and 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 22-45 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.

The invention relates to a peptide derived from p53 that could be used as a vaccine against cancer.

P53 peptide vaccine

The current invention provides improved methods and means for the treatment of virally induced intraepithelial neoplasias of the ano-genital tract, such as HPV induced vulvar-, cervical-, vaginal-, penile- and anal intraepithelial neoplasias (VIN, CIN, VAIN, PIN and AIN). The invention provides a method of treatment of a subject suffering from an anogenital intraepithelial neoplasia comprising at least the steps of first determining whether the subject has a T-cell reactivity for viral early antigens, in particular high risk type HPV antigens; and subsequently a local treatment of the neoplasia with immune modulating compounds eliciting local inflammation if the subject scores positive for the T-cell reactivity, preferably a CD4+response against HPV early antigens. The invention also comprises methods and means to induce or further stimulate a cellular immune response against HPV antigens, prior to or during treatment with the immune modulating compound capable of eliciting a local inflammatory response.

Methods and means for the treatment of HPV induced intraepithelial neoplasia

Disclosed is a method and composition for treating tumors or infectious diseases, wherein the composition includes CD40 binding molecules together with CTL-activating peptides, e.g., tumor antigens. Such composition is useful for enhancing the anti-tumor effect of a peptide tumor vaccine, or for otherwise activating CTLs so that the activated CTLs can act against tumorous or infected cells. The CD40 binding molecules can include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, (Fab')and Fv, as well as other molecules including peptides, oligonucleotides, peptidomimetics and organic compounds which bind to CD40 and activate the CTL response.

CD40 binding molecules and CTL peptides for treating tumors

The present invention provides novel methods for immunotherapy. The invention provides immune cells and methods to generate them, with the capacity to at least in part reduce an immune response in a host. In one aspect, the invention provides a method for generating a dendritic cell with the capacity to tolerize a T-cell for antigen the T-cell was specific for including culturing peripheral blood monocytes from an individual to differentiate into dendritic cells, activating the dendritic cells in the presence of a glucocorticoid hormone and loading the activated dendritic cell with the antigen the T-cell was specific for.

Dendritic cells activated in the presence of glucocorticoid hormones are capable of suppressing antigen-specific T cell 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

Rienk Offringa