TY  - JOUR
A1  - Tsoneva, Desislava
A1  - Minev, Boris
A1  - Frentzen, Alexa
A1  - Zhang, Qian
A1  - Wege, Anja K.
A1  - Szalay, Aladar A.
T1  - Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis
JF  - Molecular Therapy Oncolytics
N2  - 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 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.
KW  - humanized tumor
KW  - mouse model
KW  - subcutaneous human tumors
KW  - Oncolytic vaccinia virus
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170786
VL  - 5
ER  - 
TY  - JOUR
A1  - Riquelme, Paloma
A1  - Haarer, Jan
A1  - Kammler, Anja
A1  - Walter, Lisa
A1  - Tomiuk, Stefan
A1  - Ahrens, Norbert
A1  - Wege, Anja K.
A1  - Goecze, Ivan
A1  - Zecher, Daniel
A1  - Banas, Bernhard
A1  - Spang, Rainer
A1  - Fändrich, Fred
A1  - Lutz, Manfred B.
A1  - Sawitzki, Birgit
A1  - Schlitt, Hans J.
A1  - Ochando, Jordi
A1  - Geissler, Edward K.
A1  - Hutchinson, James A.
T1  - TIGIT\(^+\) iTregs elicited by human regulatory macrophages control T cell immunity
JF  - Nature Communications
N2  - Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4(+) T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4(+) T cells to IL-10-producing, TIGIT(+) FoxP3(+)-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-beta, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT(+) Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct-pathway Tregs.
KW  - Allotransplantation
KW  - Immunosuppression
KW  - Monocytes and macrophages
KW  - Regulatory T cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226321
VL  - 9
IS  - 9
ER  -