Targeting of 111In-Labeled Dendritic Cell Human Vaccines Improved by Reducing Number of Cells

被引：52

作者：

Aarntzen, Erik H. J. G. ^{[1
,2
,3
]}

Srinivas, Mangala ^{[1
]}

Bonetto, Fernando ^{[8
,9
]}

Cruz, Luis J. ^{[1
,5
]}

Verdijk, Pauline ^{[1
,6
]}

Schreibelt, Gerty ^{[1
]}

van de Rakt, Mandy ^{[1
]}

Lesterhuis, W. Joost ^{[2
,7
]}

van Riel, Maichel ^{[3
]}

Punt, Cornelius J. A. ^{[7
]}

Adema, Gosse J. ^{[1
]}

Heerschap, Arend ^{[4
]}

Figdor, Carl G. ^{[1
]}

Oyen, Wim J. ^{[3
]}

de Vries, I. Jolanda M. ^{[1
]}

机构：

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

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

[3] Radboud Univ Nijmegen, Dept Nucl Med, NL-6500 HB Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Dept Radiol, NL-6500 HB Nijmegen, Netherlands

[5] Leiden Univ, Med Ctr, Dept Endocrinol, Leiden, Netherlands

[6] RIVM, Dept Vaccinol, Blithoven, Netherlands

[7] Univ Amsterdam, Acad Med Ctr, Dept Med Oncol, NL-1105 AZ Amsterdam, Netherlands

[8] INTECCONICET, Santa Fe, Argentina

[9] Univ Nacl Litoral, Fac Ingn Quim, Dept Mat, Santa Fe, Argentina

来源：

CLINICAL CANCER RESEARCH | 2013年 / 19卷 / 06期

基金：

欧洲研究理事会;

关键词：

LYMPH-NODES; IN-VIVO; MELANOMA PATIENTS; IMMUNE-RESPONSES; MIGRATION; VACCINATION; IMMUNOTHERAPY; MATURATION; INJECTION; MRI;

D O I：

10.1158/1078-0432.CCR-12-1879

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Anticancer dendritic cell (DC) vaccines require the DCs to relocate to lymph nodes (LN) to trigger immune responses. However, these migration rates are typically very poor. Improving the targeting of ex vivo generated DCs to LNs might increase vaccine efficacy and reduce costs. We investigated DC migration in vivo in humans under different conditions. Experimental Design: HLA-A*02:01 patients with melanoma were vaccinated with mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (NCT00243594). For this study, patients received an additional intradermal vaccination with 111 In-labeled mature DCs. The injection site was pretreated with nonloaded, activated DCs, TNF alpha, or Imiquimod; granulocyte macrophage colony-stimulating factor was coinjected or smaller numbers of DCs were injected. Migration was measured by scintigraphy and compared with an intrapatient control vaccination. In an ex vivo tissue model, we measured CCL21-directed migration of F-19-labeled DCs over a period of up to 12 hours using F-19 MRI to supplement our patient data. Results: Pretreatment of the injection site induced local inflammatory reactions but did not improve migration rates. Both in vitro and in vivo, reduction of cell numbers to 5 x 10(6) or less cells per injection improved migration. Furthermore, scintigraphy is insufficient to study migration of such small numbers of In-111-labeled DCs in vivo. Conclusion: Reduction of cell density, not pretreatment of the injection site, is crucial for improved migration of DCs to LNs in vivo. Clin Cancer Res; 19(6); 1525-33. (C) 2013 AACR.

引用

页码：1525 / 1533

页数：9

共 29 条

[1] Skin-Test Infiltrating Lymphocytes Early Predict Clinical Outcome of Dendritic Cell-Based Vaccination in Metastatic Melanoma [J].

Aarntzen, Erik H. J. G. ;

Bol, Kalijn ;

Schreibelt, Gerty ;

Jacobs, Joannes F. M. ;

Lesterhuis, W. Joost ;

Van Rossum, Michelle M. ;

Adema, Gosse J. ;

Figdor, Carl G. ;

Punt, Cornelis J. A. ;

De Vries, I. Jolanda M. .

CANCER RESEARCH, 2012, 72 (23) :6102-6110

[2] Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3′-fluoro-3′-deoxy-thymidine ([18F]FLT) PET imaging [J].

Aarntzen, Erik H. J. G. ;

Srinivas, Mangala ;

De Wilt, Johannes H. W. ;

Jacobs, Joannes F. M. ;

Lesterhuis, W. Joost ;

Windhorst, Albert D. ;

Troost, Esther G. ;

Bonenkamp, Johannes J. ;

van Rossum, Michelle M. ;

Blokx, Willeke A. M. ;

Mus, Roel D. ;

Boerman, Otto C. ;

Punt, Cornelis J. A. ;

Figdor, Carl G. ;

Oyen, Wim J. G. ;

de Vries, I. Jolanda M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (45) :18396-18399

[3]

Angeli Veronique, 2006, Lymphatic Research and Biology, V4, P217, DOI 10.1089/lrb.2006.4406

[4] A large-scale 19F MRI-based cell migration assay to optimize cell therapy [J].

Bonetto, F. ;

Srinivas, M. ;

Weigelin, B. ;

Cruz, L. J. ;

Heerschap, A. ;

Friedl, P. ;

Figdor, C. G. ;

de Vriesa, I. J. M. .

NMR IN BIOMEDICINE, 2012, 25 (09) :1095-1103

[5] How many dendritic cells are required to initiate a T-cell response? [J].

Celli, Susanna ;

Day, Mark ;

Mueller, Andreas J. ;

Molina-Paris, Carmen ;

Lythe, Grant ;

Bousso, Philippe .

BLOOD, 2012, 120 (19) :3945-3948

[6]

de Vries IJM, 2003, CANCER RES, V63, P12

[7]

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

[8] Features Associated with Survival in Metastatic Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines [J].

Dillman, Robert O. ;

Fogel, Gary B. ;

Cornforth, Andrew N. ;

Selvan, Senthamil R. ;

Schiltz, Patric M. ;

DePriest, Carol .

CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 2011, 26 (04) :407-415

[9] Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters [J].

Engell-Noerregaard, Lotte ;

Hansen, Troels Holz ;

Andersen, Mads Hald ;

Straten, Per Thor ;

Svane, Inge Marie .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2009, 58 (01) :1-14

[10] Dendritic cell immunotherapy: mapping the way [J].

Figdor, CG ;

de Vries, IJM ;

Lesterhuis, WJ ;

Melief, CJM .

NATURE MEDICINE, 2004, 10 (05) :475-480

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