Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity

Vincenzo Russo, Arcadi Cipponi, Laura Raccosta, Cristina Rainelli, Raffaella Fontana, Daniela Maggioni, Francesca Lunghi, Sylvain Mukenge, Fabio Ciceri, Marco Bregni, Claudio Bordignon, Catia Traversari

Research output: Contribution to journalArticle

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Abstract

The exploitation of the physiologic processing and presenting machinery of DCs by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. Here we show that lymphocytes genetically modified to express self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of tyrosinase-related protein 2-transduced (TRP-2-transduced) lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice. Analysis of the mechanism responsible for the induction of such an immune response allowed us to demonstrate that cross-presentation of the antigen mediated by the CD11c+CD8α + DC subset had occurred. Furthermore, we demonstrated in vivo and in vitro that DCs had undergone activation upon phagocytosis of genetically modified lymphocytes, a process mediated by a cell-to-cell contact mechanism independent of CD40 triggering. Targeting and activation of secondary lymphoid organ-resident DCs endowed antigen-specific T cells with full effector functions, which ultimately increased tumor growth control and animal survival in a therapeutic tumor setting. We conclude that the use of transduced lymphocytes represents an efficient method for the in vivo loading of tumor-associated antigens on DCs.

Original languageEnglish
Pages (from-to)3087-3096
Number of pages10
JournalJournal of Clinical Investigation
Volume117
Issue number10
DOIs
Publication statusPublished - Oct 1 2007

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Neoplasm Antigens
Immunity
Lymphocytes
CD11c Antigens
Neoplasms
Cross-Priming
Antigens
Cancer Vaccines
Long-Term Memory
Autoantigens
Phagocytosis
T-Lymphocytes
Growth
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Russo, V., Cipponi, A., Raccosta, L., Rainelli, C., Fontana, R., Maggioni, D., ... Traversari, C. (2007). Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity. Journal of Clinical Investigation, 117(10), 3087-3096. https://doi.org/10.1172/JCI30605

Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity. / Russo, Vincenzo; Cipponi, Arcadi; Raccosta, Laura; Rainelli, Cristina; Fontana, Raffaella; Maggioni, Daniela; Lunghi, Francesca; Mukenge, Sylvain; Ciceri, Fabio; Bregni, Marco; Bordignon, Claudio; Traversari, Catia.

In: Journal of Clinical Investigation, Vol. 117, No. 10, 01.10.2007, p. 3087-3096.

Research output: Contribution to journalArticle

Russo, V, Cipponi, A, Raccosta, L, Rainelli, C, Fontana, R, Maggioni, D, Lunghi, F, Mukenge, S, Ciceri, F, Bregni, M, Bordignon, C & Traversari, C 2007, 'Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity', Journal of Clinical Investigation, vol. 117, no. 10, pp. 3087-3096. https://doi.org/10.1172/JCI30605
Russo, Vincenzo ; Cipponi, Arcadi ; Raccosta, Laura ; Rainelli, Cristina ; Fontana, Raffaella ; Maggioni, Daniela ; Lunghi, Francesca ; Mukenge, Sylvain ; Ciceri, Fabio ; Bregni, Marco ; Bordignon, Claudio ; Traversari, Catia. / Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 10. pp. 3087-3096.
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