Dendritic Cell-based Immunotherapy Pulsed With Wilms Tumor 1 Peptide and Mucin 1 as an Adjuvant Therapy for Pancreatic Ductal Adenocarcinoma After Curative Resection: A Phase I/IIa Clinical Trial

被引：28

作者：

Nagai, Kazuhiro ^{[1
]}

Adachi, Tomohiko ^{[2
]}

Harada, Hiroshi ^{[1
]}

Eguchi, Susumu ^{[2
]}

Sugiyama, Haruo ^{[3
]}

Miyazaki, Yasushi ^{[1
,4
]}

机构：

[1] Nagasaki Univ Hosp, Transfus & Cell Therapy Unit, 1-7-1 Sakamoto, Nagasaki 8528501, Japan

[2] Nagasaki Univ Hosp, Dept Surg, Nagasaki, Japan

[3] Osaka Univ, Dept Canc Immunol, Grad Sch Med, Osaka, Japan

[4] Nagasaki Univ, Atom Bomb Dis Inst, Dept Hematol, Nagasaki, Japan

来源：

ANTICANCER RESEARCH | 2020年 / 40卷 / 10期

关键词：

Pancreatic ductal adenocarcinoma; dendritic cell vaccination; WT1; MUC1; phase I/IIa study; GENE WT1; CANCER; CHEMOTHERAPY; GEMCITABINE; EXPRESSION; OVEREXPRESSION; PROGRESSION; REPRESSION; S-1;

D O I：

10.21873/anticanres.14593

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: We evaluated the safety, feasibility, and preliminary efficacy of Wilms tumor gene 1 (WT1) peptide and Mucin 1 (MUC1)-pulsed dendritic cell (DC) (WT1/MUC1-DC) vaccination as an adjuvant immunotherapy for surgically resectable pancreatic ductal adenocarcinoma (PDA) patients. Patients and Methods: Eligible patients were administered WT1/MUC1-DC vaccination at least seven times every 2 weeks with concomitant adjuvant chemotherapy after surgical resection of PDA. Results: Ten patients were enrolled and no Grade 2 or higher toxicities were associated with DC vaccination. The estimated overall survival (OS) and relapse-free survival (RFS) at 3-years from the time of surgical resection were 77.8% and 35.0%, respectively. Immunohistochemical analysis suggested a possible relationship between induction of WT1-specific cytotoxic T lymphocyte after DC vaccination and higher infiltration of CD3/CD4/CD8 lymphocytes in tumor tissues. Conclusion: WT1/MUC1-DC vaccination in the adjuvant setting was safe and well-tolerated in PDA patients after tumor resection. A large-scale prospective study is warranted to evaluate the clinical benefit of this modality.

引用

页码：5765 / 5776

页数：12

共 46 条

[1] Pancreatic cancer: Translational research aspects and clinical implications [J].

Ansari, Daniel ;

Chen, Bi-Cheng ;

Dong, Lei ;

Zhou, Meng-Tao ;

Andersson, Roland .

WORLD JOURNAL OF GASTROENTEROLOGY, 2012, 18 (13) :1417-1424

[2] Immunobiology of dendritic cells [J].

Banchereau, J ;

Briere, F ;

Caux, C ;

Davoust, J ;

Lebecque, S ;

Liu, YT ;

Pulendran, B ;

Palucka, K .

ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+

[3] ISOLATION AND CHARACTERIZATION OF A ZINC FINGER POLYPEPTIDE GENE AT THE HUMAN CHROMOSOME-11 WILMS TUMOR LOCUS [J].

CALL, KM ;

GLASER, T ;

ITO, CY ;

BUCKLER, AJ ;

PELLETIER, J ;

HABER, DA ;

ROSE, EA ;

KRAL, A ;

YEGER, H ;

LEWIS, WH ;

JONES, C ;

HOUSMAN, DE .

CELL, 1990, 60 (03) :509-520

[4] The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research [J].

Cheever, Martin A. ;

Allison, James P. ;

Ferris, Andrea S. ;

Finn, Olivera J. ;

Hastings, Benjamin M. ;

Hecht, Toby T. ;

Mellman, Ira ;

Prindiville, Sheila A. ;

Viner, Jaye L. ;

Weiner, Louis M. ;

Matrisian, Lynn M. .

CLINICAL CANCER RESEARCH, 2009, 15 (17) :5323-5337

[5] Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome [J].

de Vries, IJM ;

Bernsen, MR ;

Lesterhuis, WJ ;

Scharenborg, NM ;

Strijk, SP ;

Gerritsen, MJP ;

Ruiter, DJ ;

Figdor, CG ;

Punt, CJA ;

Adema, GJ .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (24) :5779-5787

[6] Peptide-Pulsed Dendritic Cells Have Superior Ability to Induce Immune-Mediated Tissue Destruction Compared to Peptide with Adjuvant [J].

Dissanayake, Dilan ;

Murakami, Kiichi ;

Tran, Michael D. ;

Elford, Alisha R. ;

Millar, Douglas G. ;

Ohashi, Pamela S. .

PLOS ONE, 2014, 9 (03)

[7] REPRESSION OF THE INSULIN-LIKE GROWTH FACTOR-II GENE BY THE WILMS-TUMOR SUPPRESSOR WT1 [J].

DRUMMOND, IA ;

MADDEN, SL ;

ROHWERNUTTER, P ;

BELL, GI ;

SUKHATME, VP ;

RAUSCHER, FJ .

SCIENCE, 1992, 257 (5070) :674-678

[8] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[9] Pancreatic Ductal Adenocarcinoma: A Strong imbalance of Good and Bad immunological Cops in the Tumor Microenvironment [J].

Foucher, Etienne D. ;

Ghigo, Clement ;

Chouaib, Salem ;

Galon, Jerome ;

Iovanna, Juan ;

Olive, Daniel .

FRONTIERS IN IMMUNOLOGY, 2018, 9

[10] HUMAN PLATELET-DERIVED GROWTH FACTOR-A CHAIN IS TRANSCRIPTIONALLY REPRESSED BY THE WILMS-TUMOR SUPPRESSOR WT1 [J].

GASHLER, AL ;

BONTHRON, DT ;

MADDEN, SL ;

RAUSCHER, FJ ;

COLLINS, T ;

SUKHATME, VP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10984-10988

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