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

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Blood First Edition Paper, prepublished online September 22, 2008; DOI

10.1182/blood-2008-06-165654.

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*, a Zappasodi, Carmelo tella, a Mortarini,

Serenella M Pupa, Michele Magni, Liliana Devizzi, Paola Matteucci, Paola

Baldassari, Ravagnani, Antonello Cabras, 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@... .

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