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Blood, 1 January 2009, Vol. 113, No. 1, pp. 18-27.
Prepublished online as a Blood First Edition Paper on September 22, 2008; DOI 10.1182/blood-2008-06-165654.
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Submitted June 27, 2008
Accepted August 26, 2008
Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunological responses in indolent B cell lymphoma patients with relapsed and measurable disease: a pilot study
Massimo Di Nicola*, Roberta Zappasodi, Carmelo Carlostella, Roberta Mortarini, Serenella M Pupa, Michele Magni, Liliana Devizzi, Paola Matteucci, Paola Baldassari, Fernando Ravagnani, Antonello Cabras, Andrea Anichini, and Alessandro M Gianni
"C. Gandini" Bone Marrow Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Human Tumor Immunobiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Pathology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
* Corresponding author; email: massimo.dinicola{at}istitutotumori.mi.it.
Eighteen relapsed patients with measurable indolent non-Hodgkin lymphoma (NHL) were vaccinated with dendritic cells (DCs) loaded with killed autologous tumor cells. Six patients had objective clinical responses including three continuous complete remissions (CR) and three partial responses (PR), with a median follow-up of 50.5 months. Eight patients had stable disease, while four had progressive disease. Clinical responses were significantly associated with a reduction in CD4+CD25+FOXP3+ regulatory T cells, an increase in CD3-CD56dimCD16+ NK cells and maturation of lymphocytes to the effector memory stage either in post-vaccine peripheral blood or tumor specimen samples. In partial responding patients, vaccination significantly boosted the IFN- producing T cell response to autologous tumor challenge. In one HLA-A*0201+ patient that achieved CR, IL-4 release by circulating T cells in response to tumor-specific IgH-encoded peptides was also documented. Immunohistochemical analysis of tumor biopsies using biotin-conjugated autologous serum samples revealed a tumor-restricted humoral response only in the post-vaccine serum from responding patients, whereas no autologous tumor-specific reactivity was detected in pre- or post-vaccine sera from non-responder patients. Collectively these results demonstrate that vaccination with tumor-loaded DCs may induce both T and B cell responses and produces clinical benefits in indolent NHL patients with measurable disease. This study is registered with the Instituto Superiore di Sanita: http://www.iss.it with protocol number 7578-PRE 21-801

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