Alonso-Camino, V, Rajani, K, Kottke, T et al. (11 more authors) (2014) The Profile of Tumor Antigens Which Can Be Targeted By Immunotherapy Depends Upon the Tumor's Anatomical Site. In: Molecular Therapy. 7th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), 21-24 May 2014, Washington, DC, USA. Nature Publishing Group , S200-S200.
Abstract
We have shown that VSV engineered to express a cDNA library from human melanoma cells (ASMEL, Altered Self Melanoma Epitope Library) was an effective systemic therapy for subcutaneous (s.c.) murine B16 melanomas (Pulido et al., Nat. Biotech. 2012, 30:337-43). Here we show that the combination of antigens identified from the ASMEL which successfully treated s.c. B16 tumors (VSV-N-RAS/VSV-CYT-C/VSV-TYRP-1) was completely ineffective against intra-cranial (i.c.) B16 tumors. In contrast, a different combination of VSV-expressed antigens isolated from the ASMEL (VSV-HIF-2alpha/VSV-SOX-10/VSV-C-MYC/VSV-TYRP-1) was highly effective against i.c. B16 tumors, but had no efficacy against s.c B16 tumors. Correspondingly, i.c. B16 tumors expressed a HIF-2alphaHi, SOX-10Hi, c-mycHi, TYRP1, N-RASlo CYT-Clo antigen profile, which differed significantly from the HIF-2alphalo, SOX-10lo, c-myclo, TYRP1, N-RASHi CYT-CHi phenotype of s.c. B16 tumors, and which was imposed upon the tumor cells by CD11b+ cells within the local tumor microenvironment in the brain. By combining T cell co-stimulation with systemic VSV-cDNA treatment, long term cures (>100days) of over 60% of mice with established i.c. melanomas were achieved, whereas control mice succumbed to tumor within 25-30 days. Our data show that tumors of the same histological type, but growing in different anatomical locations, represent a series of related, but antigenically distinct, ‘quasi-species’ because the site of tumor growth profoundly affects the profile of potential immunogens expressed by the tumor cells. This has important implications for the design of therapies which target the same histological type of tumor growing in different locations. the same histological type of tumor growing in different locations.
Metadata
Item Type: | Proceedings Paper |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Oncology and Clinical Research (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Jul 2016 09:40 |
Last Modified: | 04 Nov 2016 02:02 |
Published Version: | https://dx.doi.org/10.1038/mt.2014.64 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/mt.2014.64 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87580 |