Oxford Biomedica (uk) Limited

Ludwig Institute for Cancer Research Limited

Oxford University Innovation Limited

Irina Redchenko

Miles William Carroll

Adrian V S Hill

Susan Mary Kingsman

Susan Marie Kingsman

Benoit J Van Den Eynde

Carol S Leung

The invention relates to a composition for inducing a T cell mediated immune response for the treatment or prevention of prostate cancer comprising a modified Vaccinia virus Ankara (MVA) vector expressing the 5T4 antigen polypeptide under control of a poxvirus F11 promoter. Suitably said poxvirus F11 promoter is the endogenous MVA F11 promoter. More suitably said vector expresses a polypeptide having the amino acid sequence of SEQ ID NO: 1 or said vector expresses a polypeptide encoded by a polynucleotide having the nucleic acid sequence of SEQ. ID NO: 2. The invention also relates to uses and methods.

Compositions for inducing an immune response

Chimpanzee adenovirus (ChAd) and MVA virus vectors containing polynucleotide sequences encoding cancer antigens are administered sequentially to a subject in a suitable adjuvant in order to achieve a prime boost effect. The polynucleotides are expressed in situ following administration to provide a MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. Also, a hli/MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. An improved T cell response is found. In a particular synergistic therapeutic approach a triple combination of ChAdOx and MVA vectors together with chemotherapeutic agent and checkpoint inhibitor results in depleted myeloid derived suppressor cells (MDSC) and dramatically improves survival time in a mouse model of cancer.

Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer

There is provided an MHC class I peptide epitope from 5T4 antigen. In particular, there is provided a peptide epitope of 5T4 which comprises one of the following: (i) the amino acid sequence shown as SEQ ID No.2; (ii) the minimal epitope from the amino acid sequence shown as SEQ ID No.3; (iii) the minimal epitope from the amino acid sequence shown as SEQ ID No.4. (iv) the minimal epitope from the amino acid sequence shown as SEQ ID No. 5. (v) the minimal epitope from the amino acid sequence shown as SEQ ID No.6. (vi) the minimal epitope from the amino acid sequence shown as SEQ ID No.7. There is also provided a vaccine comprising such a peptide (or precursor thereof) and its use to treat and/or prevent a disease, in particular a cancerous disease.

MHC class I peptide epitopes from the human 5T4 tumor-associated antigen

There is provided an MHC class I peptide epitope from 5T4 antigen. In particular, there is provided a peptide epitope of 5T4 which comprises one of the following: (i) the amino acid sequence shown as SEQ ID No. 2; (ii) the minimal epitope from the amino acid sequence shown as SEQ ID No. 3; (iii) the minimal epitope from the amino acid sequence shown as SEQ ID No. 4. (iv) the minimal epitope from the amino acid sequence shown as SEQ ID No. 5. (v) the minimal epitope from the amino acid sequence shown as SEQ ID No. 6. (vi) the minimal epitope from the amino acid sequence shown as SEQ ID No. 7. There is also provided a vaccine comprising such a peptide (or precursor thereof) and its use to treat and/or prevent a disease, in particular a cancerous disease. There is also provided a nucleic acid molecule encoding a MHC class I peptide epitope from the human 5T4 tumor-associated antigen and vector comprising the nucleic acid molecule.

Nucleic acid molecule encoding a MHC class I peptide epitope from the human 5T4 tumor-associated antigen and vector comprising the nucleic acid molecule

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Oxford, United Kingdom

Irina Redchenko