PT  - JOURNAL ARTICLE
AU  - Oelke, Mathias
AU  - Ugel, Stefano
AU  - Zoso, Alessia
AU  - De Santo, Carmela
AU  - Li, Yu
AU  - Marigo, Ilaria
AU  - Zanovello, Paola
AU  - Scarselli, Elisa
AU  - Cipriani, Barbara
AU  - Bronte, Vincenzo
AU  - Schneck, Jonathan P.
TI  - In vivo administration of artificial Antigen Presenting Cells licenses low avidity T cells for treatment of cancer (131.13)
DP  - 2010 Apr 01
TA  - The Journal of Immunology
PG  - 131.13--131.13
VI  - 184
IP  - 1 Supplement
4099  - http://www.jimmunol.org/content/184/1_Supplement/131.13.short
4100  - http://www.jimmunol.org/content/184/1_Supplement/131.13.full
SO  - J. Immunol.2010 Apr 01; 184
AB  - The development of effective anti-tumor immune responses is normally constrained by low avidity, tumor-specific cytotoxic T lymphocytes (CTL) which are unable to eradicate the tumor. Therefore, new strategies to rescue anti-tumor activity of low avidity melanoma-specific CTL in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low avidity CTL we immunized mice bearing metastatic lung melanoma with artificial Antigen Presenting Cells (aAPC), made by covalently coupling pepMHC-Ig dimers and B7.1-Ig molecules to magnetic beads. aAPC treatment induced significant tumor reduction in a mouse telomerase antigen system and complete tumor eradication in a mouse TRP-2 antigen system, when low avidity CTL specific for these antigens were adoptively transferred. In addition, in an in vivo treatment model of subcutaneous melanoma, aAPC injection also augmented the activity of adoptively transferred CTL and significantly delayed tumor growth. In vivo tumor clearance due to aAPC administration correlated with in situ proliferation of the transferred CTL. In vitro studies showed that aAPC effectively stimulated cytokine release and TCR down-regulation in low avidity CTL. Therefore, in vivo aAPC administration represents a potentially novel approach to improve adoptive immunotherapy of cancer.