TY - JOUR
T1 - Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease
T2 - a pilot study
AU - Nicola, Massimo Di
AU - Zappasodi, Roberta
AU - Carmelo, Carlo Stella
AU - Mortarini, Roberta
AU - Pupa, Serenella M.
AU - Magni, Michele
AU - Devizzi, Liliana
AU - Matteucci, Paola
AU - Baldassari, Paola
AU - Ravagnani, Fernando
AU - Cabras, Antonello
AU - Anichini, Andrea
AU - Gianni, Alessandro M.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Eighteen relapsed patients with measurable indolent non-Hodgkin lymphoma (NHL) were vaccinated with dendritic cells (DC s) loaded with killed autologous tumor cells. Six patients had objective clinical responses including 3 continuous complete responses (CR s) and 3 partial responses (PR s), with a median follow up of 50.5 months. Eight patients had stable disease, whereas 4 had progressive disease. Clinical responses were significantly associated with a reduction in CD4 +CD25 +FOXP3 + regulatory T cells, an increase in CD3 -CD56 dimCD16 + natural killer (NK) cells, and maturation of lymphocytes to the effector memory stage in either postvaccination peripheral blood or tumor specimen samples. In partial responding patients, vaccination significantly boosted the IFN- γ-producing Tcell response to autologous tumor challenge. In one HLA-Aandz.ast;0201 + patient who achieved CR, IL-4 release by circulating T cells in response to tumor-specific IgHencoded peptides was also documented. Immunohistochemical analysis of tumor biopsies using biotin-conjugated autologous serum samples revealed a tumorrestricted humoral response only in the postvaccination serum from responding patients. Collectively these results demonstrate that vaccination with tumorloaded 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 Istituto Superiore di Sanità: http://www.iss.it with protocol number 7578-PRE 21-801. (Blood. 2009;113:18-27).
AB - Eighteen relapsed patients with measurable indolent non-Hodgkin lymphoma (NHL) were vaccinated with dendritic cells (DC s) loaded with killed autologous tumor cells. Six patients had objective clinical responses including 3 continuous complete responses (CR s) and 3 partial responses (PR s), with a median follow up of 50.5 months. Eight patients had stable disease, whereas 4 had progressive disease. Clinical responses were significantly associated with a reduction in CD4 +CD25 +FOXP3 + regulatory T cells, an increase in CD3 -CD56 dimCD16 + natural killer (NK) cells, and maturation of lymphocytes to the effector memory stage in either postvaccination peripheral blood or tumor specimen samples. In partial responding patients, vaccination significantly boosted the IFN- γ-producing Tcell response to autologous tumor challenge. In one HLA-Aandz.ast;0201 + patient who achieved CR, IL-4 release by circulating T cells in response to tumor-specific IgHencoded peptides was also documented. Immunohistochemical analysis of tumor biopsies using biotin-conjugated autologous serum samples revealed a tumorrestricted humoral response only in the postvaccination serum from responding patients. Collectively these results demonstrate that vaccination with tumorloaded 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 Istituto Superiore di Sanità: http://www.iss.it with protocol number 7578-PRE 21-801. (Blood. 2009;113:18-27).
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U2 - 10.1182/blood-2008-06-165654
DO - 10.1182/blood-2008-06-165654
M3 - Article
C2 - 18809757
AN - SCOPUS:59449108329
VL - 113
SP - 18
EP - 27
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -