In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer

Stefano Ugel, Alessia Zoso, Carmela De Santo, Yu Li, Ilaria Marigo, Paola Zanovello, Elisa Scarselli, Barbara Cipriani, Mathias Oelke, Jonathan P. Schneck, Vincenzo Bronte

Research output: Contribution to journalArticle

Abstract

The development of effective antitumor immune responses is normally constrained by low-avidity, tumor-specific CTLs that are unable to eradicate the tumor. Strategies to rescue antitumor activity of low-avidity melanoma-specific CTLs in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low-avidity CTLs, we immunized mice bearing lung melanoma metastases 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 CTLs 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 CTLs 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, enhanced CTL-mediated lysis, and TCR down-regulation in low-avidity CTLs. Therefore, in vivo aAPC administration represents a potentially novel approach to improve cancer immunotherapy.

Original languageEnglish
Pages (from-to)9376-9384
Number of pages9
JournalCancer Research
Volume69
Issue number24
DOIs
Publication statusPublished - Dec 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Ugel, S., Zoso, A., De Santo, C., Li, Y., Marigo, I., Zanovello, P., Scarselli, E., Cipriani, B., Oelke, M., Schneck, J. P., & Bronte, V. (2009). In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer. Cancer Research, 69(24), 9376-9384. https://doi.org/10.1158/0008-5472.CAN-09-0400