immune system
• over 95 % of the CD8 T cells present in circulation express the transgenic TCR that is specific for the H2-Db restricted epitope of Silv (gp100), a protein that is highly expressed in melanoma cells
• these transgenic T cells constitute about 20% of spleen cells
• the baseline levels of activation markers for the transgenic T cells indicate that most of cells are in a nave state
|
• upon in vitro stimulation with the immunogenic epitope of gp100, CD8 T cells are activated and proliferate extensively
|
• CD 8 T cells produce large amounts of IFN-gamma when cultured in the presence of melanoma cells
• large number of IFN-gamma producing CD8 T cells are found in melanoma tumors that have regressed due to treatment with gp100 vaccine, IL-2, and adoptive transfer of transgenic CD8 T cells
|
neoplasm
• despite the presence of large number of anti-gp100 CD8 T cells, transplanted melanoma tumors that express gp100 have the same growth kinetics as tumors transplanted into control mice
• adoptive transfer of transgenic splenocytes into normal mice bearing melanoma tumors also has no effect on tumor growth
• there is a modest delay in tumor growth when mice that are recipients of transgenic T cells are also vaccinated with peptides that mimic the gp100 epitope
• when IL-2 is administered with the vaccine, there is a large regression in tumor size in mice that are also recipients of transgenic T cells
• mice bearing melanoma tumors that receive vaccine, transgenic T cells, and IL-2 have survival times of over 1 year compared to controls that die within 2 months
|
hematopoietic system
• over 95 % of the CD8 T cells present in circulation express the transgenic TCR that is specific for the H2-Db restricted epitope of Silv (gp100), a protein that is highly expressed in melanoma cells
• these transgenic T cells constitute about 20% of spleen cells
• the baseline levels of activation markers for the transgenic T cells indicate that most of cells are in a nave state
|
• upon in vitro stimulation with the immunogenic epitope of gp100, CD8 T cells are activated and proliferate extensively
|