title: The profile of tumor antigens which can be targeted by immunotherapy depends upon the tumor's anatomical site.
abstract: Previously, we showed that vesicular stomatitis virus (VSV) engineered to express a cDNA library from human melanoma cells (ASMEL, Altered Self Melanoma Epitope Library) was an effective systemic therapy to treat subcutaneous (s.c.) murine B16 melanomas. Here, we show that intravenous treatment with the same ASMEL VSV-cDNA library was an effective treatment for established intra-cranial (i.c.) melanoma brain tumors. The optimal combination of antigens identified from the ASMEL which treated s.c. B16 tumors (VSV-N-RAS+VSV-CYTC-C+VSV-TYRP-1) was ineffective against i.c. B16 brain tumors. In contrast, combination of VSV-expressed antigens-VSV-HIF-2α+VSV-SOX-10+VSV-C-MYC+VSV-TYRP1-from ASMEL which was highly effective against i.c. B16 brain tumors, had no efficacy against the same tumors growing subcutaneously. Correspondingly, i.c. B16 tumors expressed a HIF-2α(Hi), SOX-10(Hi), c-myc(Hi), TYRP1, N-RAS(lo)Cytc(lo) antigen profile, which differed significantly from the HIF-2α(lo), SOX-10(lo), c-myc(lo), TYRP1, N-RAS(Hi)Cytc(Hi) phenotype of s.c. B16 tumors, and was imposed upon the tumor cells by CD11b(+) cells within the local brain tumor microenvironment. Combining T-cell costimulation with systemic VSV-cDNA treatment, long-term cures of mice with established i.c. tumors were achieved in about 75% of mice. Our data show that the anatomical location of a tumor profoundly affects the profile of antigens that it expresses.
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Vanesa
authors: V
authors: Alonso-Camino
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Karishma
authors: K
authors: Rajani
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Timothy
authors: T
authors: Kottke
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Diana
authors: D
authors: Rommelfanger-Konkol
authors: 1] Department of Molecular Medicine, The Institute of Cancer Research, London, UK [2] The Institute of Cancer Research, Division of Cancer Biology, Chester Beatty Laboratories, London, UK.
authors: Shane
authors: S
authors: Zaidi
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Jill
authors: J
authors: Thompson
authors: 1] Department of Molecular Medicine, The Institute of Cancer Research, London, UK [2] Department of Ophthalmology and Ocular Oncology Mayo Clinic, Rochester, Minnesota, USA.
authors: Jose
authors: J
authors: Pulido
authors: Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors: Elizabeth
authors: E
authors: Ilett
authors: Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors: Oliver
authors: O
authors: Donnelly
authors: Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors: Peter
authors: P
authors: Selby
authors: Leggett Building, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
authors: Hardev
authors: H
authors: Pandha
authors: Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors: Alan
authors: A
authors: Melcher
authors: The Institute of Cancer Research, Division of Cancer Biology, Chester Beatty Laboratories, London, UK.
authors: Kevin
authors: K
authors: Harrington
authors: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors: Rosa Maria
authors: RM
authors: Diaz
authors: 1] Department of Molecular Medicine, The Institute of Cancer Research, London, UK [2] Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, Leeds, UK [3] Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Richard
authors: R
authors: Vile
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D015723:Gene Library; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment; D018116:Vesiculovirus / Q000235:genetics* / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor