OBJECTIVES: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.
OBJECTIVES: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS:Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.
Authors: Nicola R Hardwick; Paul Frankel; Christopher Ruel; Julie Kilpatrick; Weimin Tsai; Ferdynand Kos; Teodora Kaltcheva; Lucille Leong; Robert Morgan; Vincent Chung; Raechelle Tinsley; Melissa Eng; Sharon Wilczynski; Joshua D I Ellenhorn; Don J Diamond; Mihaela Cristea Journal: Clin Cancer Res Date: 2018-01-04 Impact factor: 12.531
Authors: Nicola R Hardwick; Mary Carroll; Teodora Kaltcheva; Dajun Qian; Dean Lim; Lucille Leong; Peiguo Chu; Joseph Kim; Joseph Chao; Marwan Fakih; Yun Yen; Jonathan Espenschied; Joshua D I Ellenhorn; Don J Diamond; Vincent Chung Journal: Clin Cancer Res Date: 2014-07-01 Impact factor: 12.531
Authors: Timothy L Frankel; William Burns; John Riley; Richard A Morgan; Jeremy L Davis; Kenichi Hanada; Martha Quezado; Steven A Rosenberg; Richard E Royal Journal: Cancer Immunol Immunother Date: 2010-08-24 Impact factor: 6.968