1. Enhancing CTL responses to melanoma cell vaccines in vivo : synergistic increases obtained using IFNγ primed and IFNβ treated B7‐1 + B16‐F10 melanoma cells
- Author
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Stephen John Ralph, Irene Hatzinisiriou, and Shala Dezfouli
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Immunology ,Antigen presentation ,Priming (immunology) ,Receptors, Cell Surface ,Lymphocyte Activation ,Major histocompatibility complex ,Cancer Vaccines ,Cell Line ,Interferon-gamma ,Mice ,Antigen ,T-Lymphocyte Subsets ,Interferon ,medicine ,Animals ,Humans ,Immunology and Allergy ,Interferon gamma ,Melanoma ,biology ,business.industry ,Histocompatibility Antigens Class I ,Interferon-beta ,Cell Biology ,Intercellular Adhesion Molecule-1 ,Mice, Inbred C57BL ,Disease Models, Animal ,B7-1 Antigen ,Cancer research ,biology.protein ,Cancer vaccine ,business ,Neoplasm Transplantation ,CD8 ,T-Lymphocytes, Cytotoxic ,medicine.drug - Abstract
Sequentially treating human melanoma cell lines by priming with interferon-gamma before adding interferon-beta was previously found to be the most efficient protocol for producing concurrently increased expression of the three surface antigens B7-1, intercellular adhesion molecule-1 and human histocompatibility leucocyte antigens Class I. The present study describes similar outcomes when the same sequential intercellular adhesion molecule-based protocol is applied to murine B16-F10 melanoma cells as well as preclinical studies using the B16-F10 model as a poorly immunogenic melanoma. Thus, treating B16-F10 cells or a highly expressing B7-1 transfected subline (B16-F10/B7-1 hi) by priming with interferon-gamma for 24 h before adding interferon-beta for a further 48 h (interferon-gamma 72/beta 48) increased expression of all three surface antigens, particularly major histocompatibility complex class I whose increased expression was sustained for several days. As a whole tumour cell vaccine, interferon-gamma 72/beta 48 treated B16-F10 cells produced greater levels of cytoxic T lymphocyte response compared to vaccines prepared from cells treated with a single type of interferon. Furthermore, B16-F10 cells expressing high levels of B7-1 and treated using the interferon-gamma 72/beta 48 protocol (interferon-gamma 72/beta 48-treated B16-F10/B7-1 hi) produced substantially increased cytoxic T lymphocyte responses with a fivefold greater synergy than the combined results of either interferon treated or B7-1 expressing cells tested individually. The resulting CD8+ cytoxic T lymphocyte showed greater specificity for B16-F10 cells with tenfold higher killing than for syngeneic EL-4 lymphoma cells. Killing proceeded via the perforin-mediated pathway. CTL responses were induced independent of CD4+ T helper cells. The majority of mice receiving interferon-gamma 72/beta 48-treated B16-F10/B7-1 hi vaccine in vivo remained tumour free after challenge with 5 x 105 live B16-F10 cells expressing intermediate B7-1 levels. The novel strategy described will help enhance vaccine potency when applied clinically to prepare whole cell based cancer vaccine therapies.
- Published
- 2003
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