Sensitivity of Breast Tumors to Oncolytic Viruses

2006 ◽  
Author(s):  
Maryam Ahmed
2021 ◽  
Vol 22 (2) ◽  
pp. 477
Author(s):  
Guendalina Froechlich ◽  
Chiara Gentile ◽  
Luigia Infante ◽  
Carmen Caiazza ◽  
Pasqualina Pagano ◽  
...  

Background: HER2-based retargeted viruses are in advanced phases of preclinical development of breast cancer models. Mesothelin (MSLN) is a cell-surface tumor antigen expressed in different subtypes of breast and non-breast cancer. Its recent identification as a marker of some triple-negative breast tumors renders it an attractive target, presently investigated in clinical trials employing antibody drug conjugates and CAR-T cells. The availability of MSLN-retargeted oncolytic viruses may complement the current immunotherapeutic panel of biological drugs against HER2-negative breast and non-breast tumors. Methods: A fully virulent, tumor-targeted oncolytic Herpes simplex virus-1 (MSLN-THV) with a selectivity for mesothelin-expressing cancer cells was generated. Recombineering technology was used to replace an essential moiety of the viral glycoprotein D with antibody fragments derived from clinically validated MSLN monoclonal antibodies, and to allow IL12 cargo expression in infected cells. Panels of breast and female reproductive system cell lines were used to verify the oncolytic potential of the viral constructs. A platform for production of the retargeted viruses was developed in HEK 293 cells, providing stable expression of a suitable chimeric receptor. Results: We demonstrated the selectivity of viral infection and cytotoxicity by MSLN-retargeted viruses in a panel of mesothelin-positive cancer cells, originating from breast and female reproductive system tumors. We also developed a second-generation oncolytic MSLN-THV, encoding IL12, to enhance the immunotherapeutic potential of the viral backbone. A non-tumor cell line expressing a chimeric MSLN/Nectin-1 receptor, de-sensitized from antiviral responses by genetic inactivation of the Stimulator of Interferon Genes (STING)-dependent pathway was engineered, to optimize viral yields. Conclusions: Our proof-of-concept study proposes MSLN-retargeted herpesviruses as potential cancer immunotherapeutics for assessments in preclinical models of MSLN-positive tumors, complementing the available panel of oncolytic viruses to HER2-negative breast tumors.


Author(s):  
A Ciurea ◽  
A Arpasteuan ◽  
G Dindelegan ◽  
R Motocu ◽  
L Rogojan

2020 ◽  
pp. 25-31
Author(s):  
M. L. Mazo ◽  
O. E. Jacobs ◽  
O. S. Puchkova ◽  
M. V. Feldsherov ◽  
E. V. Kondratyev

The rate of detection of breast cancer by MRI, while other methods of radiological diagnosis are not sufficiently informative, ranges from 5.2 to 26.3 per cent. Suspicious breast tumors of category BI-RADS 4, 5 show morphological image-guided biopsy verification, in particular MRI with contrast. Purpose. To show the possibilities and features of carrying out MRI-guided vacuum breast biopsy, including after aesthetic breast augmentation. Material and methods. A comprehensive X-ray, ultrasound and MRI examination of 54 women aged between 28 and 70 years with different breast tumors was conducted. Of these, five were detected only by breast MRI with contrast, and were morphologically verified by MRI-guided vacuum aspiration biopsy. Results. 14 of the 54 patients with breast mass were diagnosed with breast cancer and 26 were diagnosed with benign diseases. The effectiveness of comprehensive examination and low-invasive high-tech MRI-guided procedures in early refined screening for breast cancer, including after aesthetic breast augmentation, has been demonstrated. MRI-guided vacuum-assisted breast biopsy is a fast, safe and accurate diagnostic method of morphological verification of suspicious breast tumors that do not have X-ray and ultrasound.


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