scholarly journals PARP Targeted Alpha-Particle Therapy Enhances Response to PD-1 Immune-Checkpoint Blockade in a Syngeneic Mouse Model of Glioblastoma

2021 ◽  
Vol 4 (1) ◽  
pp. 344-351
Author(s):  
Hannah Dabagian ◽  
Tahereh Taghvaee ◽  
Paul Martorano ◽  
Daniel Martinez ◽  
Minu Samanta ◽  
...  
Keyword(s):  
Mouse Model ◽  
Alpha Particle ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Particle Therapy ◽  
Syngeneic Mouse ◽  
Syngeneic Mouse Model

scholarly journals Immune Checkpoint Blockade Improves Chemotherapy in the PyMT Mammary Carcinoma Mouse Model

2020 ◽  
Vol 10 ◽  
Author(s):  
Evelyn Sirait-Fischer ◽  
Catherine Olesch ◽  
Annika F. Fink ◽  
Matthias Berkefeld ◽  
Arnaud Huard ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mammary Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

Abstract 5031: A humanized mouse model for translational assessment of targeted immune checkpoint blockade

2015 ◽  
Author(s):  
Gilson Baia ◽  
David Vasquez-Dunddel ◽  
Daniel Ciznadija ◽  
David Sidransky ◽  
Amanda Katz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Humanized Mouse ◽  
Humanized Mouse Model

Abstract 3228: Immune checkpoint blockade and autoimmune diseases: Development of a mouse model of colitis induced by anti-CTLA-4

2019 ◽  
Author(s):  
Edwige Nicodeme ◽  
Florence Blandel ◽  
Valerie Boullay ◽  
Yannick Saintillan ◽  
Gael Krysa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Autoimmune Diseases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

Abstract B075: Modeling response and resistance to immune checkpoint blockade in syngeneic mouse glioma

2019 ◽  
Author(s):  
Katrin Deumelandt ◽  
Jens Blobner ◽  
Jana K. Sonner ◽  
Mirco Friedrich ◽  
Edward Green ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Syngeneic Mouse ◽  
Mouse Glioma

scholarly journals Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

2020 ◽  
Author(s):  
Simona Camorani ◽  
Margherita Passariello ◽  
Lisa Agnello ◽  
Silvia Esposito ◽  
Francesca Collina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Lung Metastases ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Syngeneic Mouse Model

Abstract Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy, the current major option for treatment. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers that may allow for novel combination therapies with immune-checkpoint blockade in TNBC. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in mesenchymal invasive TNBC, both on tumor cells and tumor microenvironment (TME). We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC.Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays on PDGFRβ-positive cells. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAbs combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAbs-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in a syngeneic mouse model by acting on both TME and cancer cells. Conclusion: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.

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