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Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis
Please always quote using this URN: urn:nbn:de:bvb:20-opus-170786
- Oncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells wasOncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells was observed. We also demonstrated successful in vivo colonization of such tumors with systemically administered VACVs. Further, a new recombinant GLV-1h376 VACV encoding for a secreted human CTLA4-blocking single-chain antibody (CTLA4 scAb) was tested. Surprisingly, although proving CTLA4 scAb’s in vitro binding ability and functionality in cell culture, beside the significant increase of CD56\(^{bright}\) NK cell subset, GLV-1h376 was not able to increase cytotoxic T or overall NK cell levels at the tumor site. Importantly, the virus-encoded β-glucuronidase as a measure of viral titer and CTLA4 scAb amount was demonstrated. Therefore, studies in our “patient-like” humanized tumor mouse model allow the exploration of newly designed therapy strategies considering the complex relationships between the developing tumor, the oncolytic virus, and the human immune system.…
Author: | Desislava Tsoneva, Boris Minev, Alexa Frentzen, Qian Zhang, Anja K. Wege, Aladar A. Szalay |
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URN: | urn:nbn:de:bvb:20-opus-170786 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie | |
Language: | English |
Parent Title (English): | Molecular Therapy Oncolytics |
Year of Completion: | 2017 |
Volume: | 5 |
Pagenumber: | 41-61 |
Source: | Molecular Therapy Oncolytics 2017, Vol. 5, 41-61. DOI: 10.1016/j.omto.2017.03.001 |
DOI: | https://doi.org/10.1016/j.omto.2017.03.001 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28480327 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 572 Biochemie |
Tag: | Oncolytic vaccinia virus; humanized tumor; mouse model; subcutaneous human tumors |
Release Date: | 2019/10/10 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |