719P - Dendritic cell vaccination in combination with OK432, gemcitabine and/or S-1 in patients with advanced pancreatic or biliary tract cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Cytotoxic agents
Hepatobiliary Cancers
Immunotherapy
Therapy
Biological therapy
Presenter Masahiro Ogasawara
Authors M. Ogasawara, S. Ota
  • Internal Medicine, Sapporo Hokuyu Hospital, 003-0006 - Sapporo/JP

Abstract

Background

Although dendritic cells (DCs) are potent antigen presenting cells that can generate T cells specific to tumor antigens, efficacy of immunotherapy using DCs is so far limited. To improve the efficacy of this modality, we conducted a clinical trial of DC vaccination in combination with gemcitabine (GEM) and/or S-1 for patients with advanced pancreatic or biliary tract cancer. The advantages of using these drugs are immunomodulatory functions including the inhibition of regulatory T cells (Tregs). OK432, a toll like receptor (TLR) 4 agonist, was employed to enhance activation of DCs both in vitro and in vivo.

Methods

31 patients (17 males, 14 females; aged 27-81 years, median 61 years) with advanced pancreatic (24) or biliary tract (7) cancer refractory to standard treatment were treated with DC vaccination in combination with OK432 and GEM and/or S-1 from 2009 to 2011. Autologous DCs were generated from adherent mononuclear cells using standard protocols. Wilms' tumor 1 (WT1) and/or MUC1 peptide-loaded mature DCs were administered intradermally every 2 weeks for 7 times. Induction of vaccine-induced T cell responses was monitored using HLA-tetramer assays.

Results

The treatment was well tolerated and none of the patients experienced more than grade 3 adverse events during the treatment period. Of 31 patients, 5 patients had partial response (PR), 14 had stable disease (SD), 2 had mixed response and 10 had progressive disease following one course of the treatment. Median overall survival was 289 days for all patients, which was longer than that of the patients treated with GEM and/or S-1.Survival of patients achieving PR or SD (responder) after one course of DC vaccination was longer than those who did not respond to the treatment (p < 0.01). Increased numbers of cancer antigen-specific cytotoxic T cells and decreased numbers of Tregs was observed in responders after one course of treatment.

Conclusions

DC vaccine-based immunotherapy combined with a TLR agonist and chemotherapy was demonstrated to be safe and more effective in patients with advanced pancreatic or biliary tract cancer compared with chemotherapy alone.

Disclosure

All authors have declared no conflicts of interest.