In Vivo Studies of Radiolabeled Monoclonal Antibodies Mc5 and KC4 in Human Breast Cancer

Author(s):  
Paul A. Bunn ◽  
David G. Dienhart ◽  
Raymond F. Schmelter ◽  
James L. Lear ◽  
Gary Miller ◽  
...  
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  

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]


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1606
Author(s):  
Walaa Alharbi ◽  
Iftekhar Hassan ◽  
Rais Ahmad Khan ◽  
Shazia Parveen ◽  
Khadijah H. Alharbi ◽  
...  

Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC50 value of 7.8 ± 0.4 μM compared to 2 (less active, IC50 ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.


2018 ◽  
Vol Volume 11 ◽  
pp. 185-191 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Marco Cascella ◽  
Domenica Rea ◽  
Giuseppe Palma ◽  
...  

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