T cells and bifunctional protein against human papillomavirus

Recombinant T cell clonotypes are provided that express T cell receptor alpha and T cell receptor beta polypeptides with specificity for human papillomavirus (HPV) type 16 E6 protein and that amplify in response to a therapeutic vaccine and traffic to ovarian lesional tissue in a patient whose HPV lesions regressed in response to the vaccine. Recombinant T cells expressing appropriate TCR alpha and beta complimentarity determining sequences for HPV 16 E6 binding and treating HPV-cased cancers are provided. Bifunctional proteins having TCR alpha and beta segments that bind to HPV 16 E6 residues 91-115 and a single chain Fv anti-CD3 antibody domain are provided. These bifunctional proteins can direct T cells to HPV-infected cells.

ABSTRACT

Recombinant T cell clonotypes are provided that express T cell receptor alpha and T cell receptor beta polypeptides with specificity for human papillomavirus (HPV) type 16 E6 protein and that amplify in response to a therapeutic vaccine and traffic to ovarian lesional tissue in a patient whose HPV lesions regressed in response to the vaccine. Recombinant T cells expressing appropriate TCR alpha and beta complimentarity determining sequences for HPV 16 E6 binding and treating HPV-cased cancers are provided. Bifunctional proteins having TCR alpha and beta segments that bind to HPV 16 E6 residues 91-115 and a single chain Fv anti-CD3 antibody domain are provided. These bifunctional proteins can direct T cells to HPV-infected cells.

CLAIMS

1. A plurality of isolated recombinant human T cells enriched for recombinant human T cells comprising a recombinant T cell receptor beta (TCRB) gene encoding CDR3 sequence CASS PTS GGLTWDEQYF (SEQ ID NO:1) or CASSHNSGREGNEQFF (SEQ ID NOG) or CASSFPGENEQFF (SEQ ID NOG) or CASSWEAGQETQYF (SEQ ID NO:4).

PATENT INFORMATION


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