Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progres...Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progress has been made in developing targeted therapies for breast cancer,</span> <span style="font-family:Verdana;">advanced breast cancer continues to have high mortality, with poor 5-year</span> <span style="font-family:Verdana;">survival rates. Thus, current therapies are insufficient in treating advanced</span><span style="font-family:Verdana;"> stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber </span><span style="font-family:Verdana;">to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We</span> <span style="font-family:Verdana;">showed that the modified virus targets and infects CXCR4- and CXCR7-</span><span style="font-family:Verdana;">overexpressing breast cancer cells more efficiently than a wild-type control</span><span style="font-family:Verdana;"> vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.展开更多
文摘Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progress has been made in developing targeted therapies for breast cancer,</span> <span style="font-family:Verdana;">advanced breast cancer continues to have high mortality, with poor 5-year</span> <span style="font-family:Verdana;">survival rates. Thus, current therapies are insufficient in treating advanced</span><span style="font-family:Verdana;"> stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber </span><span style="font-family:Verdana;">to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We</span> <span style="font-family:Verdana;">showed that the modified virus targets and infects CXCR4- and CXCR7-</span><span style="font-family:Verdana;">overexpressing breast cancer cells more efficiently than a wild-type control</span><span style="font-family:Verdana;"> vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.
