This Article Full Text Full Text (PDF) Correction (v67,p12034) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nanni, P. Articles by Lollini, P.-L. Search for Related Content PubMed PubMed Citation Articles by Nanni, P. Articles by Lollini, P.-L.

Antimetastatic Activity of a Preventive Cancer Vaccine

¹ Section of Cancer Research, University of Bologna; ² Laboratory of Oncologic Research, Rizzoli Orthopaedic Institutes, Bologna, Italy; ³ National Institute for Cancer Research, Genoa, Italy; and ⁴ Aging Research Center, Chieti, Italy

Requests for reprints: Pier-Luigi Lollini, Sezione di Cancerologia, Viale Filopanti 22, 40126 Bologna, Italy. Phone: 39-051241110; Fax: 39-051242169; E-mail: pierluigi.lollini{at}unibo.it.

The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a >99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN- and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma. [Cancer Res 2007;67(22):11037–44]

This article has been cited by other articles:

				Correction: Antimetastatic Activity of a Preventive Cancer Vaccine Cancer Res., December 15, 2007; 67(24): 12034 - 12034. [Full Text] [PDF]