title: Tumor-specific Ab-mediated targeting of MHC-peptide complexes induces regression of human tumor xenografts in vivo.
abstract: A cancer immunotherapy strategy is described herein that combines the advantage of the well established tumor targeting capabilities of high-affinity recombinant fragments of Abs with the known efficient, specific, and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC-peptide complexes. Structurally, it consists of a previously uncharacterized class of recombinant chimerical molecules created by the genetic fusion of single-chain (sc) Fv Ab fragments, specific for tumor cell surface antigens, to monomeric scHLA-A2 complexes containing immunodominant tumor- or viral-specific peptides. The fusion protein can induce very efficiently tumor cell lysis, regardless of the expression of self peptide-MHC complexes. Moreover, these molecules exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results suggest that recombinant scFv-MHC-peptide fusion molecules could represent an approach to immunotherapy, bridging Ab and T lymphocyte attack on cancer cells.
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Lev
authors.forename: Roy
authors.initials: R
authors.lastname: Noy
authors.forename: Kfir
authors.initials: K
authors.lastname: Oved
authors.forename: Hila
authors.initials: H
authors.lastname: Novak
authors.forename: Dina
authors.initials: D
authors.lastname: Segal
authors.forename: Peter
authors.initials: P
authors.lastname: Walden
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Yoram
authors.initials: Y
authors.lastname: Reiter
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D000922:Immunotoxins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D010455:Peptides; D011993:Recombinant Fusion Proteins