Novel Immunocompetent Murine Tumor Model for Evaluation of Conditionally Replication-Competent (Oncolytic) Murine Adenoviral Vectors

ABSTRACT Oncolytic adenoviral vectors that express immunostimulatory transgenes are currently being evaluated in clinic. Preclinical testing of these vectors has thus far been limited to immunodeficient xenograft tumor models since human adenoviruses do not replicate effectively in murine tumor cells. The effect of the immunostimulatory transgene on overall virus potency can therefore not be readily assessed in these models. Here, a model is described that allows the effective testing of mouse armed oncolytic adenovirus (MAV) vectors in immunocompetent syngeneic tumor models. These studies demonstrate that the MAV vectors have a high level of cytotoxicity in a wide range of murine tumor cells. The murine oncolytic viruses were successfully armed with murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) by a novel method which resulted in vectors with a high level of tumor-specific transgene expression. The mGM-CSF-armed MAV vectors showed an improved level of antitumor potency and induced a systemic antitumor immune response that was greater than that induced by unarmed parental vectors in immunocompetent syngeneic tumor models. Thus, the oncolytic MAV-1 system described here provides a murine homolog model for the testing of murine armed oncolytic adenovirus vectors in immunocompetent animals. The model allows evaluation of the impact of virus replication and the host immune response on overall virus potency and enables the generation of translational data that will be important for guiding the clinical development of these viruses.

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NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽

10.3390/cancers13122999 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2999

Author(s):

Deborah Reynaud ◽

Roland Abi Nahed ◽

Nicolas Lemaitre ◽

Pierre-Adrien Bolze ◽

Wael Traboulsi ◽

...

Keyword(s):

Immune Response ◽

Tumor Cells ◽

Major Gene ◽

Critical Role ◽

Orthotopic Model ◽

Independent Manner ◽

Maternal Immune Response ◽

The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

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Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19980717)77:2<306::aid-ijc22>3.0.co;2-7 ◽

1998 ◽

Vol 77 (2) ◽

pp. 306-313 ◽

Cited By ~ 27

Author(s):

Alexandra Treister ◽

Orit Sagi-Assif ◽

Michal Meer ◽

Nechama I. Smorodinsky ◽

Romema Anavi ◽

...

Keyword(s):

Tumor Cells ◽

Growth Conditions ◽

Murine Tumor ◽

Murine Tumor Cells

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Echinococcus multilocularis: In vitro secretion of antigen by hybridomas from metacestode germinal cells and murine tumor cells

Experimental Parasitology ◽

10.1016/0014-4894(89)90096-9 ◽

1989 ◽

Vol 68 (2) ◽

pp. 186-191 ◽

Cited By ~ 8

Author(s):

Angela Dieckmann-Schuppert ◽

Andreas Ruppel ◽

Reinhard Burger ◽

Werner Frank

Keyword(s):

Tumor Cells ◽

Echinococcus Multilocularis ◽

Murine Tumor ◽

Germinal Cells ◽

Murine Tumor Cells

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Identification of the alpha IIb beta 3 integrin in murine tumor cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)41927-8 ◽

1992 ◽

Vol 267 (24) ◽

pp. 17314-17320

Author(s):

Y.Q. Chen ◽

X Gao ◽

J Timar ◽

D Tang ◽

I.M. Grossi ◽

...

Keyword(s):

Tumor Cells ◽

Murine Tumor ◽

Murine Tumor Cells

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A Combretastatin-Mediated Decrease in Neutrophil Concentration in Peripheral Blood and the Impact on the Anti-Tumor Activity of This Drug in Two Different Murine Tumor Models

PLoS ONE ◽

10.1371/journal.pone.0110091 ◽

2014 ◽

Vol 9 (10) ◽

pp. e110091 ◽

Cited By ~ 5

Author(s):

Anja Bille Bohn ◽

Thomas Wittenborn ◽

Anne Sofie Brems-Eskildsen ◽

Tinne Laurberg ◽

Lotte Bonde Bertelsen ◽

...

Keyword(s):

Peripheral Blood ◽

Tumor Models ◽

Murine Tumor ◽

The Impact ◽

Anti Tumor Activity

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Preclinical assessment of anti-tumor activity and immune response in syngeneic tumor models

European Journal of Cancer ◽

10.1016/s0959-8049(16)32887-8 ◽

2016 ◽

Vol 69 ◽

pp. S97

Author(s):

M. Franklin ◽

M. Thayer ◽

D. Draper ◽

D. Saims ◽

S. Wise

Keyword(s):

Immune Response ◽

Tumor Models ◽

Syngeneic Tumor ◽

Anti Tumor Activity

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Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Journal of Clinical Medicine ◽

10.3390/jcm9041185 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1185 ◽

Cited By ~ 3

Author(s):

Martha Baydoun ◽

Olivier Moralès ◽

Céline Frochot ◽

Colombeau Ludovic ◽

Bertrand Leroux ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Response ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cells ◽

Surgical Techniques ◽

Ovarian Cancer Cells ◽

The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

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