scholarly journals Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8+T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

2014 ◽  
Vol 15 (1) ◽  
pp. 265-271 ◽  
Author(s):  
Chun-Hui Yuan ◽  
Xue-Qin Yang ◽  
Cheng-Liang Zhu ◽  
Shao-Ping Liu ◽  
Bi-Cheng Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cancer Model ◽  
Ifn Gamma ◽  
Interleukin 7 ◽  
Breast Cancer Model ◽  
Anti Tumor Activity

Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model

2014 ◽  
Vol 349 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Lucia Borriello ◽  
Matthieu Montès ◽  
Yves Lepelletier ◽  
Bertrand Leforban ◽  
Wang-Qing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Anti Tumor Activity

scholarly journals Osteopontin binds ICOSL promoting tumor metastasis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Raineri ◽  
Chiara Dianzani ◽  
Giuseppe Cappellano ◽  
Federica Maione ◽  
Gianluca Baldanzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Metastasis ◽  
Immune Checkpoints ◽  
Cancer Model ◽  
Therapeutic Approaches ◽  
Breast Cancer Model ◽  
4T1 Breast Cancer ◽  
Anti Tumor Activity

Abstract ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio.

scholarly journals 702 TJ-CD4B (ABL111), a Claudin18.2-targeted 4-1BB tumor engager induces potent tumor-dependent immune response without dose-limiting toxicity in preclinical studies

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A730-A730
Author(s):  
Wenqing Jiang ◽  
Zhengyi Wang ◽  
Zhen Sheng ◽  
Jaeho Jung ◽  
Taylor Guo
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Gene Expression Analysis ◽  
Cell Activation ◽  
Clinical Development ◽  
Cynomolgus Monkeys ◽  
Anti Tumor Activity

Background4-1BB (CD137) is a co-stimulatory receptor that stimulates the function of multiple immune cells. Its ability to induce potent anti-tumor activity makes 4-1BB an attractive target for immuno-oncology. However, clinical development of a monospecific 4-1BB agonistic antibody has been hampered by dose-limiting hepatic toxicities. To minimize systemic toxicities, we have developed a novel Claudin18.2 (CLDN18.2) x 4-1BB bispecific antibody, TJ-CD4B (ABL111) that stimulates 4-1BB pathway only when it engages with Claudin 18.2, a tumor-associated antigen specifically expressed in gastrointestinal cancers. TJ-CD4B (ABL111) is now being evaluated in patients with advanced solid tumors in a first-in-human trial (NCT04900818).MethodsTJ-CD4B (ABL111) was evaluated in vivo using the human 4-1BB knock-in mice bearing CLDN18.2 expressing MC38 tumor cells. Pharmacodynamic effects upon treatment were characterized in tumor tissue and blood. Immunophenotyping of the tumor microenvironment (TME) and peripheral blood was performed by flow cytometry. Soluble biomarkers were measured using Luminex-based multiplex assay. In-depth gene expression analysis was performed on primary human CD8+ T cells that were co-cultured with CLDN18.2 expressing cells in the presence of anti-CD3 using NanoString nCounter®. Pharmacokinetic (PK) and toxicity study were performed in cynomolgus monkeys.ResultsTJ-CD4B (ABL111) elicited complete tumor regression in 13 out of 18 MC38 tumor bearing mice given at a dose above 2 mg/kg. Dose-dependent anti-tumor activity was associated with enhanced T cell activation in TME and expansion of memory T cells in the peripheral blood. Increased CD8+ T cells number and proliferation were observed in both tumor nest and surrounding stroma while the level of soluble 4-1BB in the serum was also elevated in response to the treatment. In vitro gene expression analysis by Nanostring revealed TJ-CD4B(ABL111) effectively activated immune pathways characterized by IFN?-signaling and T cell inflammation. Preclinically, TJ-CD4B was well tolerated at the repeated doses up to 100 mg/kg/wk in cynomolgus monkeys without the adverse influence on the liver function which is generally affected by 4-1BB activation. Besides, no cytokine release or immune activation was observed in the periphery.ConclusionsTJ-CD4B (ABL111) is a novel CLDN18.2 dependent 4-1BB bispecific agonist antibody that induced T cell activation and memory response in tumor with CLDN18.2 expression, leading to a strong anti-tumor activity in vivo. TJ-CD4B did not induce systemic immune response nor hepatic toxicity due to the CLDN18.2 dependent 4-1BB stimulation. These data warrant the current clinical development in phase I trial to validate the safety properties and tumor specific responses.

Impact of histamine H4 receptor deficiency on the modulation of T cells in a murine breast cancer model

2020 ◽  
Author(s):  
Melisa B. Nicoud ◽  
Mónica A. Táquez Delgado ◽  
María de la Paz Sarasola ◽  
Agustina Vidal ◽  
Daniela Speisky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Model ◽  
Histamine H4 Receptor ◽  
Breast Cancer Model ◽  
H4 Receptor

Therapeutic monoclonal antibodies target phenotypically-differing human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Human Breast ◽  
Breast Cancer Model ◽  
Cancer Tissues

13510 Background: CD44 (an adhesion molecule and stem cell antigen), CD59 (a complement-inhibitory molecule), MCSP (an adhesion and cell-cell interactions), and Trop-2 (EpCam a related signaling molecule) represent a group of biologically-significant cancer proteins acting through distinct mechanisms. We have described Abs with in vitro and in vivo cancer suppressive activity to this group of targets. However, their effectiveness depends on the phenotype of malignant cells; cell response should correlate with expression of its Ag, and tumor cells represent a heterogeneous group of non-synchronous cells. The present study describes the efficacy of those antibodies in breast cancer models and the prevalence of their antigen targets in a survey of human breast cancer tissues. Methods: In vivo activity of antibodies ARH460–16–2 (anti-CD44), AR36A36.11.1 (anti-CD59), AR11BD-2E11–2 (anti-MCSP), and AR47A6.4.2 (anti-Trop-2) in estrogen-dependent and hormone sensitive xenograft models of human breast cancer was examined. In addition, distribution of the antigens in breast cancer was determined by immunohistochemistry using tumor tissue arrays of breast cancer sections from distinct patients. Results: Treatment of an established breast cancer model with ARH460–16–2 resulted in 51% median tumor xenograft suppression (p<0.05), as well as increased survival in an MDA-MB-231 (breast cancer) grafted model. 63% of human breast cancer sections expressed the CD44 antigen. Treatment with anti-CD59 antibody AR36A36.11.1 resulted in 68% xenograft tumor suppression (p<0.005). AR47A6.4.2 anti-Trop-2 antibody bound to 100% of human breast cancer sections tested, and showed efficacy in the estrogen- dependent MCF-7 breast cancer model. Anti-MCSP antibody AR11BD-2E11–2 demonstrated 80% tumor growth inhibition (p<0.001), increased survival in an estrogen-dependent model of breast cancer, and was found to stain 62% of breast cancer tissues examined. Conclusions: The heterogeneity of breast cancer cell phenotypes in in vitro and in vivo studies and variable composite cellular antigen targets is the basis for the therapeutic use of multiple antibodies, each with independent mechanisms of action, and offers a rationale for combined antibody therapy in selected patients. [Table: see text]

scholarly journals In Vivo Lymphatic Imaging of a Human Inflammatory Breast Cancer Model

2014 ◽  
Vol 5 (9) ◽  
pp. 774-783 ◽  
Author(s):  
Germaine D. Agollah ◽  
Grace Wu ◽  
Eva M. Sevick-Muraca ◽  
Sunkuk Kwon
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Lymphatic Imaging

In vivo Performance of a Ruthenium-cyclopentadienyl Compound in an Orthotopic 1 Triple Negative Breast Cancer Model

2016 ◽  
Vol 16 (999) ◽  
pp. 1-1 ◽  
Author(s):  
Nuno Mendes ◽  
Francisco Tortosa ◽  
Andreia Valente ◽  
Fernanda Marques ◽  
António Matos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Model ◽  
Breast Cancer Model
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