Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study.
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 3 continuous complete responses (CRs) and 3 partial responses (PRs), 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(dim)CD16(+) 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-gamma-producing T-cell response to autologous tumor challenge. In one HLA-A*0201(+) patient who 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 postvaccination serum from responding 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 Istituto Superiore di Sanità: http://www.iss.it with protocol number 7578-PRE 21-801.
Di Nicola
Massimo
M
C. Gandini Medical Oncology, Bone Marrow Transplantation Unit, Fondazione Istituti di ricovero e Cura a Carattere Scientifico, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, Milan, Italy. massimo.dinicola@istitutotumori.mi.it
Zappasodi
Roberta
R
Carlo-Stella
Carmelo
C
Mortarini
Roberta
R
Pupa
Serenella M
SM
Magni
Michele
M
Devizzi
Liliana
L
Matteucci
Paola
P
Baldassari
Paola
P
Ravagnani
Fernando
F
Cabras
Antonello
A
Anichini
Andrea
A
Gianni
Alessandro M
AM
D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011786:Quality Control; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D019496:Cancer Vaccines