Hirooka Yoshiki, Itoh Akihiro, Kawashima Hiroki, Hara Kazuo, Nonogaki Koji, Kasugai Toshifumi, Ohno Eizaburo, Ishikawa Takuya, Matsubara Hiroshi, Ishigami Masatoshi, Katano Yoshiaki, Ohmiya Naoki, Niwa Yasumasa, Yamamoto Koji, Kaneko Toru, Nieda Mie, Yokokawa Kiyoshi, Goto Hidemi
Department of Endoscopy, Nagoya University, Nagoya City, Japan.
Pancreas. 2009 Apr;38(3):e69-74. doi: 10.1097/MPA.0b013e318197a9e3.
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.
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.
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.
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.
树突状细胞(DC)疗法常常能诱导可测量的免疫反应。然而,只有少数患者出现临床反应,推测这是由于能够根除肿瘤细胞的抗原特异性细胞毒性T淋巴细胞(CTL)扩增不足所致。为提高基于DC的疫苗接种的治疗效果,我们开展了第一项针对无法手术的局部晚期胰腺癌患者的吉西他滨(GEM)与免疫疗法联合治疗的临床试验。
患者(n = 5)接受了一个疗程的治疗,包括第1天静脉注射1000 mg/m²的GEM,以及在内镜超声引导下将OK432脉冲DCs细针注射到肿瘤中,随后在第4天静脉输注用抗CD3单克隆抗体刺激的淋巴因子激活的杀伤细胞(CD3-LAKs),每2周进行一次。
在研究期间未观察到严重的治疗相关不良事件。5名患者中有3名对该临床试验表现出有效反应;1名部分缓解,2名疾病长期稳定超过6个月。在部分缓解的患者中,已证明基于DC的疫苗接种联合GEM给药可诱导肿瘤抗原特异性CTL。
这种联合疗法被认为具有协同效应,可能在胰腺癌治疗中对诱导肿瘤抗原特异性CTL发挥作用。