Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors

被引:47
作者
Tamir, Ayala
Basaglia, Ernesto
Kagahzian, Arash
Jiao, Long
Jensen, Steen
Nicholls, Joanna
Tate, Paul
Stamp, Gordon
Farzaneh, Farzin
Harrison, Phillip
Stauss, Hans
George, Andrew J. T.
Habib, Nagy
Lechler, Robert I.
Lombardi, Giovanna
机构
[1] Guys Kings & St Thomas Sch Med, Guys Hosp, Kings Coll London, Dept Nephrol & Transplantat,Immunoregulat Lab, London SE1 9RT, England
[2] Kings Coll London, Dept Med, London WC2R 2LS, England
[3] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Surg Oncol & Technol, Liver Surg Sect, London W12 0HS, England
[4] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Histopathol, London W12 0HS, England
基金
英国医学研究理事会;
关键词
dendritic cells; carcinoembryonic antigen (CEA); immunotherapy;
D O I
10.1007/s00262-007-0299-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Dendritic cells (DCs) are the most effective antigen-presenting cells. In the last decade, the use of DCs for immunotherapy of cancer patients has been vastly increased. High endocytic capacity together with a unique capability of initiating primary T-cell responses have made DCs the most potent candidates for this purpose. Although DC vaccination occasionally leads to tumor regression, clinical efficacy, and immunogenicity of DCs in clinical trials has not been yet clarified. The present study evaluated the safety and effectiveness of tumor-lysate loaded DC vaccines in advanced colorectal cancer (CRC) patients with carcinoembryonic antigen (CEA) positive tumors. Results Six patients HLA-A*0201-positive were vaccinated with autologous DCs loaded with tumor lysates (TL) together with tetanus toxoid antigen, hepatitis B, and influenza matrix peptides. Two additional patients were injected with DCs that were generated from their sibling or parent with one haplotype mismatch. All patients received the vaccines every 2 weeks, with a total of three intra-nodal injections per patient. The results indicated that DC vaccination was safe and well tolerated by the patients. Specific immune responses were detected and in some patients, transient stabilization or even reduction of CEA levels were observed. The injection of haplotype mismatched HLA-A*0201-positive DCs resulted in some enhancement of the anti-tumor response in vitro and led to stabilization/reduction of CEA levels in the serum, compared to the use of autologous DCs. Conclusion Altogether, these results suggest that TL-pulsed DCs may be an effective vaccine method in CRC patients. Elimination of regulatory mechanisms as well as adjustment of the vaccination protocol may improve the efficacy of DC vaccination.
引用
收藏
页码:2003 / 2016
页数:14
相关论文
共 75 条
[1]   Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines [J].
Arroyo, JC ;
Gabilondo, F ;
Llorente, L ;
Meraz-Ríos, MA ;
Sánchez-Torres, C .
JOURNAL OF CLINICAL IMMUNOLOGY, 2004, 24 (01) :86-96
[2]   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
[3]  
Banchereau J, 2001, CANCER RES, V61, P6451
[4]   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-+
[5]   Dendritic cells generated in the presence of interferon-α stimulate allogeneic CD4+ T-cell proliferation:: modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells [J].
Carbonneil, C ;
Saidi, H ;
Donkova-Petrini, V ;
Weiss, L .
INTERNATIONAL IMMUNOLOGY, 2004, 16 (07) :1037-1052
[6]   Defective dendritic cell function in HIV-infected patients receiving effective highly active antiretroviral therapy:: Neutralization of IL-10 production and depletion of CD4+CD25+ T cells restore high levels of HIV-specific CD4+ T cell responses induced by dendritic cells generated in the presence of IFN-α [J].
Carbonneil, C ;
Donkova-Petrini, V ;
Aouba, A ;
Weiss, L .
JOURNAL OF IMMUNOLOGY, 2004, 172 (12) :7832-7840
[7]   Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA) [J].
Chakrabarti, R ;
Chang, YG ;
Song, K ;
Prud'homme, GJ .
VACCINE, 2004, 22 (9-10) :1199-1205
[8]  
Cole D J, 2000, Clin Lung Cancer, V1, P227, DOI 10.3816/CLC.2000.n.006
[9]   IL-4 protects tumor cells from anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins [J].
Conticello, C ;
Pedini, F ;
Zeuner, A ;
Patti, M ;
Zerilli, M ;
Stassi, G ;
Messina, A ;
Peschle, C ;
De Maria, R .
JOURNAL OF IMMUNOLOGY, 2004, 172 (09) :5467-5477
[10]   Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro [J].
Correale, P ;
Cusi, MG ;
Del Vecchio, MT ;
Aquino, A ;
Prete, S ;
Tsang, KY ;
Micheli, L ;
Nencini, C ;
La Placa, M ;
Montagnani, F ;
Terrosi, C ;
Caraglia, M ;
Formica, V ;
Giorgi, G ;
Bonmassar, E ;
Francini, G .
JOURNAL OF IMMUNOLOGY, 2005, 175 (02) :820-828