Synthetic CD4+ T cell-targeted antigen-presenting cells elicit protective antitumor responses

Caserta, Stefano, Alessi, Patrizia, Guarnerio, Jlenia, Basso, Veronica and Mondino, Anna (2008) Synthetic CD4+ T cell-targeted antigen-presenting cells elicit protective antitumor responses. Cancer Research, 68 (8). pp. 3010-3018. ISSN 0008-5472

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CD4(+) helper T cells are critical for protective immune responses and yet suboptimally primed in response to tumors. Cell-based vaccination strategies are under evaluation in clinical trials but limited by the need to derive antigen-presenting cells (APC) from patients or compatible healthy donors. To overcome these limitations, we developed CD4(+) T cell-targeted synthetic microbead-based artificial APC (aAPC) and used them to activate CD4(+) T lymphocytes specific for a tumor-associated model antigen (Ag) directly from the naive repertoire. In vitro, aAPC specifically primed Ag-specific CD4(+) T cells that were activated to express high levels of CD44, produced mainly interleukin 2, and could differentiate into Th1-like or Th2-like cells in combination with polarizing cytokines. I.v. administration of aAPC led to Ag-specific CD4(+) T-cell activation and proliferation in secondary lymphoid organs, conferred partial protection against subcutaneous tumors, and prevented the establishment of lung metastasis. Taken together, our data support the use of cell-free, synthetic aAPC as a specific and versatile alternative to expand peptide-specific CD4(+) T cells in adoptive and active immunotherapy.

Item Type: Article
Keywords: cancer immunotherapy; vaccination; T cells
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Global Health and Infection
Subjects: Q Science > QR Microbiology > QR0180 Immunology
R Medicine > RM Therapeutics. Pharmacology > RM0270 Immunotherapy. Serotherapy
Depositing User: Stefano Caserta
Date Deposited: 30 Sep 2015 07:00
Last Modified: 21 Sep 2017 13:55
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