Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells
| Autor: | Carl G. Figdor, Harm Westdorp, Sander Kelderman, Winald R. Gerritsen, Katja Petry, Christian U. Blank, Marieke E. B. Welzen, Willeke A. M. Blokx, Nicole M. Scharenborg, Michel A.M. Olde Nordkamp, Jurjen Tel, Gregor Winkels, Mandy W.M.M. van de Rakt, Kalijn F. Bol, I. Jolanda M. de Vries, Jeanette M. Pots, Erik H.J.G. Aarntzen, Rutger H. T. Koornstra, Sandra Croockewit, Gerty Schreibelt, Florian Wimmers, Annemiek J. de Boer, Roel Mus, Cornelis J. A. Punt, Joannes F M Jacobs, Michelle M. van Rossum, Tjitske Duiveman-de Boer, Tom G. M. van Oorschot |
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| Přispěvatelé: | CCA -Cancer Center Amsterdam, Oncology |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Myeloid medicine.medical_treatment Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] CD8-Positive T-Lymphocytes Cancer Vaccines Disease-Free Survival Monocytes 03 medical and health sciences Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2] Interferon-gamma Immune system Antigens Neoplasm Lysosomal-Associated Membrane Protein 1 medicine Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] Humans Neoplasm Metastasis Chemokine CCL4 Melanoma Aged business.industry Tumor Necrosis Factor-alpha Vaccination Cancer Immunotherapy Dendritic cell Dendritic Cells Middle Aged medicine.disease Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] 030104 developmental biology medicine.anatomical_structure Oncology Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] Immunology Female business CD8 Ex vivo Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | Clinical cancer research, 22(9), 2155-2166. American Association for Cancer Research Inc. Clinical Cancer Research, 22, 9, pp. 2155-2166 Clinical Cancer Research, 22, 2155-2166 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro–generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c+ myeloid DCs, naturally circulating in the blood. Experimental Design: Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c+ myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100. Results: Our results show that therapeutic vaccination against melanoma with small amounts (3–10 × 106) of myeloid DCs is feasible and without substantial toxicity. Four of 14 patients showed long-term progression-free survival (12–35 months), which directly correlated with the development of multifunctional CD8+ T-cell responses in three of these patients. In particular, high CD107a expression, indicative for cytolytic activity, and IFNγ as well as TNFα and CCL4 production was observed. Apparently, these T-cell responses are essential to induce tumor regression and promote long-term survival by stalling tumor growth. Conclusions: We show that vaccination of metastatic melanoma patients with primary myeloid DCs is feasible and safe and results in induction of effective antitumor immune responses that coincide with improved progression-free survival. Clin Cancer Res; 22(9); 2155–66. ©2015 AACR. |
| Databáze: | OpenAIRE |
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