This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Caserta, S. Articles by Mondino, A. PubMed PubMed Citation Articles by Caserta, S. Articles by Mondino, A.

Synthetic CD4⁺ T Cell–Targeted Antigen-Presenting Cells Elicit Protective Antitumor Responses

¹ Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute; and ² Università Vita-Salute San Raffaele, Milan, Italy

Requests for reprints: Anna Mondino, Cancer Immunotherapy and Gene Therapy Program, S. Raffaele Scientific Institute, Via Olgettina, 58, 20132 Milan, Italy. Phone: +390226434801; Fax: +390226434844. E-mail: anna.mondino{at}hsr.it.

Key Words: Helper T cells • Antigen presentation • Cell proliferation • Immunotherapy

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-ike 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. [Cancer Res 2008;68(8):3010–8]