A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer

被引:73
作者
Rong, Yefei [1 ]
Qin, Xia [2 ]
Jin, Dayong [1 ]
Lou, Wenhui [1 ]
Wu, Lili [2 ]
Wang, Dansong [1 ]
Wu, Wenchuan [1 ]
Ni, Xiaolin [1 ]
Mao, Zhengfa [1 ]
Kuang, Tiantao [1 ]
Zang, Ying Qin [3 ]
Qin, Xinyu [1 ]
机构
[1] Fudan Univ, Dept Gen Surg, Zhongshan Hosp, Pancreat Canc Grp, Shanghai 200433, Peoples R China
[2] Jiao Tong Univ, Sch Med, Inst Immunol, Biotherapy Ctr, Shanghai 200030, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China
关键词
Dendritic cell; MUC1; Immunotherapy; Pancreatic cancer; IMMUNE-RESPONSE; ADENOCARCINOMA; IMMUNOTHERAPY; INDUCTION; VACCINE; GAMMA;
D O I
10.1007/s10238-011-0159-0
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The objectives of this study were to assess the toxicity and immunological response induced by the intradermal (i.d.) administration of MUC1-peptide-pulsed dendritic cells (DCs) in advanced pancreatic cancer patients. Patients with recurrent lesions or metastasis after surgery, and immunohistochemistry positive for MUC1 were treated in cohorts that received 3-6 x 10(6) DCs i.d. for three or four vaccines. Each vaccine was composed of autologus DCs pulsed with MUC1-peptide. Peripheral blood mononuclear cells (PBMCs) that harvested 2 weeks after the second immunization were compared with PBMCs obtained before treatment for immunological response. Serial ELISPOT assays of PBMCs for antitumor reactivity were performed. Three patients received all four vaccines, and four patients received three vaccines. These patients were evaluable for toxicity and immunological monitoring. There were no grade 3 or 4 toxicities associated with the vaccines or major evidence of autoimmunity. Interferon-gamma and granzyme B ELISPOT assay reactivity increased significantly in 2 of 7 patients (P < 0.05). The administration of MUC1-peptide-pulsed DCs is non-toxic and capable of inducing immunological response to tumor antigen MUC1 in advanced pancreatic cancer patients. Additional studies are necessary to improve tumor rejection responses.
引用
收藏
页码:173 / 180
页数:8
相关论文
共 25 条
[1]   Adjuvant therapy for pancreatic adenocarcinoma: What have we learned since 1985? [J].
Abrams, RA .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2003, 56 (04) :3-9
[2]  
[Anonymous], 2006, SEER CANC STAT REV 1
[3]   Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery [J].
Asavaroengchai, W ;
Kotera, Y ;
Mulé, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (02) :931-936
[4]   Dendritic cells as therapeutic vaccines against cancer [J].
Banchereau, J ;
Palucka, AK .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (04) :296-306
[5]   INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR HAVE A ROLE IN TUMOR REGRESSIONS MEDIATED BY MURINE CD8+ TUMOR-INFILTRATING LYMPHOCYTES [J].
BARTH, RJ ;
MULE, JJ ;
SPIESS, PJ ;
ROSENBERG, SA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (03) :647-658
[6]  
Chang AE, 2002, CLIN CANCER RES, V8, P1021
[7]   Dendritic cell immunotherapy: mapping the way [J].
Figdor, CG ;
de Vries, IJM ;
Lesterhuis, WJ ;
Melief, CJM .
NATURE MEDICINE, 2004, 10 (05) :475-480
[8]   Dendritic cells in cancer immunotherapy [J].
Fong, L ;
Engleman, EG .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :245-273
[9]   Dendritic cells injected via different routes induce immunity in cancer patients [J].
Fong, L ;
Brockstedt, D ;
Benike, C ;
Wu, L ;
Engleman, EG .
JOURNAL OF IMMUNOLOGY, 2001, 166 (06) :4254-4259
[10]   Antigen presentation and T cell stimulation by dendritic cells [J].
Guermonprez, P ;
Valladeau, J ;
Zitvogel, L ;
Théry, C ;
Amigorena, S .
ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :621-667