Academic Journal
Preclinical evaluation of IL2-based immunocytokines supports their use in combination with dacarbazine, paclitaxel and TNF-based immunotherapy
| العنوان: | Preclinical evaluation of IL2-based immunocytokines supports their use in combination with dacarbazine, paclitaxel and TNF-based immunotherapy |
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| المؤلفون: | Pretto, Francesca, Elia, Giuliano, id_orcid:0 000-0001-8216-9560, Castioni, Nadia, Neri, Dario, id_orcid:0 000-0001-5234-7370 |
| المصدر: | Cancer Immunology, Immunotherapy, 63 (9) |
| بيانات النشر: | Springer |
| سنة النشر: | 2014 |
| المجموعة: | ETH Zürich Research Collection |
| مصطلحات موضوعية: | Immunocytokines, Interleukin-2, Oncofetal fibronectin, Vascular targeting |
| الوصف: | Antibody-cytokine fusion proteins (“immunocytokines”) represent a promising class of armed antibody products, which allow the selective delivery of potent pro-inflammatory payloads at the tumor site. The antibody-based selective delivery of interleukin-2 (IL2) is particularly attractive for the treatment of metastatic melanoma, an indication for which this cytokine received marketing approval from the US Food and drug administration. We used the K1735M2 immunocompetent syngeneic model of murine melanoma to study the therapeutic activity of F8–IL2, an immunocytokine based on the F8 antibody in diabody format, fused to human IL2. F8–IL2 was shown to selectively localize at the tumor site in vivo, following intravenous administration, and to mediate tumor growth retardation, which was potentiated by the combination with paclitaxel or dacarbazine. Combination treatment led to a substantially more effective tumor growth inhibition, compared to the cytotoxic drugs used as single agents, without additional toxicity. Analysis of the immune infiltrate revealed a significant accumulation of CD4+ T cells 24 h after the administration of the combination. The fusion proteins F8–IL2 and L19–IL2, specific to the alternatively spliced extra domain A and extra domain B of fibronectin respectively, were also studied in combination with tumor necrosis factor (TNF)-based immunocytokines. The combination treatment was superior to the action of the individual immunocytokines and was able to eradicate neoplastic lesions after a single intratumoral injection, a procedure that is being clinically used for the treatment of Stage IIIC melanoma. Collectively, these data reinforce the rationale for the use of IL2-based immunocytokines in combination with cytotoxic agents or TNF-based immunotherapy for the treatment of melanoma patients. ; ISSN:0340-7004 ; ISSN:1432-0851 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/000340877600004; http://hdl.handle.net/20.500.11850/84566 |
| DOI: | 10.3929/ethz-b-000084566 |
| الاتاحة: | https://hdl.handle.net/20.500.11850/84566 https://doi.org/10.3929/ethz-b-000084566 |
| Rights: | info:eu-repo/semantics/openAccess ; http://rightsstatements.org/page/InC-NC/1.0/ ; In Copyright - Non-Commercial Use Permitted |
| رقم الانضمام: | edsbas.469FAC18 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000084566 |
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