Bn Immunotherapeutics, Inc.

Pharmexa A/s

Iben Dalum

Søren Mouritsen

Klaus Gregorius Nielsen

Lucilla Steinaa

Anand Gautam

Dana Leach

Gunilla Karlsson

Peter Birk Rasmussen

Jesper Haaning

Martin Roland Jensen

Henrik Elsner

Peter Birk

Jesper Hanning

A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Methods for therapeutic vaccination

A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

A modified human TNF&#x3b1; molecule is capable of raising neutralizing antibodies towards unmodified human TNF&#x3b1; following administration of the modified TNF&#x3b1; to a human host, wherein one or more peptide fragments of the human TNF&#x3b1; molecule has been substituted by one or more peptides containing immunodominant T cell epitopes or a truncated form of the molecule containing the immunodominant epitope and one or both flanking regions of the human TNF&#x3b1;-molecule containing at least one TNF&#x3b1; B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of any one of the strands of the front &#x3b2;-sheet, in any one of the connecting loops, or in any one of the B', I, or D strands of the back &#x3b2;-sheet.

Modified TNF-alpha molecules, DNA encoding such and vaccines comprising such modified TNF-alpha and DNA

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Hørsholm, Denmark

Iben Dalum