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

Academisch Ziekenhuis Leiden

Isa Pharmaceuticals B.v.

Other

Leiden University Medical Center

Leids Universitair Medisch Centrum

Cornelis Johannes Maria Melief

Rienk Offringa

Sjoerd Henricus Van Der Burg

Gemma G Kenter

Annemieke M De Jong

Maria Johanna Philomena Schoenmaekers-Welters

Annemieke Geluk

Sjoerd Hendrikus Van Der Burg

Tom H M Ottenhoff

Jan Wouter Drijfhout

Selina Khan

Gijsbert Arie Van Der Marel

Reinaldus Everardus Maria Toes

Marieke Griffioen

Ferdinand Antonius Ossendorp

Jan Kessler

Dmitri Viktorovitsj Filippov

Rene Everardus Maria Toes

Theodorus Jozef Maria Helmerhorst

Delphine Gabrielle Josette Rea

Tom H M Ottenhorf

Sjoerd Hendricus Van Der Burg

Tom Henricus Maria Ottenhof

Sjoerd Henricus Postzone K1-P Van Der Burg

The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.

HPV epitopes targeted by T cells infiltrating cervical malignancies for use in vaccines

The invention relates to a peptide having a length of no more than 100 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of the human PRAME protein, wherein the peptide comprises at least one HLA class II epitope and at least one HLA class I epitope from the amino acid sequence of the human PRAME protein and to its use as such or in a composition as a medicament for the treatment and/or prevention of cancer.

PRAME derived peptides and immunogenic compositions comprising these

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 directed to a compound according to the formula [1] wherein Rand Rare branched or straight groups having up to 17 atoms selected from carbon, nitrogen, oxygen and sulphur, n is 0 to and including 18, Y is sulphur or selene, X is S or O and R is &#x2014;OH or an organic group comprising one or more peptides, one or more nucleic acids, one or more antibodies or combinations thereof. The invention is also directed to process for preparing said compound and the use of said compound as an adjuvant. The invention is also directed to a composition comprising said compound and the use of said composition, for example as a vaccine composition.

Adjuvant compound

The invention relates to the use of a peptide derived from HPV-E2, E6 and/or E7 protein for the manufacture of a medicament for the treatment or prevention of an HPV related disease, wherein the medicament is for intradermal administration.

Intradermal HPV peptide vaccination

Prame derived peptides and immunogenic compositions comprising these

The invention is directed to a compound according to the formula [1] wherein Rand Rare branched or straight groups having up to 17 atoms selected from carbon, nitrogen, oxygen and sulphur, n is 0 to and including 18, Y is sulphur or selene, X is S or 0 and R is &#x2014;OH or an organic group comprising one or more peptides, one or more nucleic acids, one or more antibodies or combinations thereof. The invention is also directed to process for preparing said compound and the use of said compound as an adjuvant. The invention is also directed to a composition comprising said compound and the use of said composition, for example as a vaccine composition.

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

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

Haarlem, Netherlands

Cornelis Johannes Maria Melief