A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients

被引：51

作者：

Lesterhuis, W. J. ^{[1
]}

de Vries, I. J. M. ^{[2
]}

Aarntzen, E. A. ^{[1
]}

de Boer, A. ^{[2
]}

Scharenborg, N. M. ^{[2
]}

van de Rakt, M. ^{[2
]}

van Spronsen, D-J ^{[3
]}

Preijers, F. W. ^{[4
]}

Figdor, C. G. ^{[2
]}

Adema, G. J. ^{[2
]}

Punt, C. J. A. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Dept Tumor Immunol, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[3] Canisius Wilhelmina Hosp Nijmegen, Dept Internal Med, NL-6500 GS Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Hematol Lab, NL-6500 HB Nijmegen, Netherlands

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 103卷 / 09期

关键词：

colon cancer; chemotherapy; dendritic cells; immunotherapy; oxaliplatin; vaccination; T-CELLS; CARCINOEMBRYONIC ANTIGEN; ANTITUMOR-ACTIVITY; MELANOMA; PEPTIDE; 5-FLUOROURACIL; IMMUNOTHERAPY; CHEMOIMMUNOTHERAPY; IRINOTECAN; CARCINOMA;

D O I：

10.1038/sj.bjc.6605935

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system. METHODS: Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs. RESULTS: In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished. CONCLUSION: The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy. British Journal of Cancer (2010) 103, 1415-1421. doi: 10.1038/sj.bjc.6605935 www.bjcancer.com Published online 5 October 2010 (C) 2010 Cancer Research UK

引用

页码：1415 / 1421

页数：7

共 29 条

[1] Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy [J].

Apetoh, Lionel ;

Ghiringhelli, Francois ;

Tesniere, Antoine ;

Obeid, Michel ;

Ortiz, Carla ;

Criollo, Alfredo ;

Mignot, Gregoire ;

Maiuri, M. Chiara ;

Ullrich, Evelyn ;

Saulnier, Patrick ;

Yang, Huan ;

Amigorena, Sebastian ;

Ryffel, Bernard ;

Barrat, Franck J. ;

Saftig, Paul ;

Levi, Francis ;

Lidereau, Rosette ;

Nogues, Catherine ;

Mira, Jean-Paul ;

Chompret, Agnes ;

Joulin, Virginie ;

Clavel-Chapelon, Francoise ;

Bourhis, Jean ;

Andre, Fabrice ;

Delaloge, Suzette ;

Tursz, Thomas ;

Kroemer, Guido ;

Zitvogel, Laurence .

NATURE MEDICINE, 2007, 13 (09) :1050-1059

[2] Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer [J].

Bourquin, C ;

Schreiber, S ;

Beck, S ;

Hartmann, G ;

Endres, S .

INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (11) :2790-2795

[3] Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients [J].

Correale, P ;

Cusi, MG ;

Tsang, KY ;

Del Vecchio, MT ;

Marsili, S ;

La Placa, M ;

Intrivici, C ;

Aquino, A ;

Micheli, L ;

Nencini, C ;

Ferrari, F ;

Giorgi, G ;

Bonmassar, E ;

Francini, G .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (35) :8950-8958

[4] 5-fluorouracil-based chemotherapy enhances the antitumor activity of a thymidylate synthase-directed polyepitopic peptide vaccine [J].

Correale, P ;

Del Vecchio, MT ;

Di Genova, G ;

Savellini, GG ;

La Placa, M ;

Terrosi, C ;

Vestri, M ;

Urso, R ;

Lemonnier, F ;

Aquino, A ;

Bonmassar, E ;

Giorgi, G ;

Francini, G ;

Cusi, MG .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2005, 97 (19) :1437-1445

[5] Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted, CEA-peptide-specific cytotoxic T cells in vitro [J].

Correale, P ;

Aquino, A ;

Giuliani, A ;

Pellegrini, M ;

Micheli, L ;

Cusi, MG ;

Nencini, C ;

Petrioli, R ;

Prete, S ;

De Vecchis, L ;

Turriziani, M ;

Giorgi, G ;

Bonmassar, E ;

Francini, G .

INTERNATIONAL JOURNAL OF CANCER, 2003, 104 (04) :437-445

[6] In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients [J].

De Vries, I. J. M. ;

Bernsen, M. R. ;

van Geloof, W. L. ;

Scharenborg, N. M. ;

Lesterhuis, W. J. ;

Rombout, P. D. M. ;

Van Muijen, G. N. P. ;

Figdor, C. G. ;

Punt, C. J. A. ;

Ruiter, D. J. ;

Adema, G. J. .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2007, 56 (10) :1667-1676

[7] Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy [J].

de Vries, IJM ;

Lesterhuis, WJ ;

Barentsz, JO ;

Verdijk, P ;

van Krieken, JH ;

Boerman, OC ;

Oyen, WJG ;

Bonenkamp, JJ ;

Boezeman, JB ;

Adema, GJ ;

Bulte, JWM ;

Scheenen, TWJ ;

Punt, CJA ;

Heerschap, A ;

Figdor, CG .

NATURE BIOTECHNOLOGY, 2005, 23 (11) :1407-1413

[8] 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

[9] Phenotypical and functional characterization of clinical grade dendritic cells [J].

de Vries, IJM ;

Eggert, AAO ;

Scharenborg, NM ;

Vissers, JLM ;

Lesterhuis, WJ ;

Boerman, OC ;

Punt, CJA ;

Adema, BJ ;

Figdor, CG .

JOURNAL OF IMMUNOTHERAPY, 2002, 25 (05) :429-438

[10]

de Vries IJM, 2003, CLIN CANCER RES, V9, P5091

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