Targeting circulating monocytes with CCL2-loaded liposomes armed with an oncolytic adenovirus

Area of Science:

• Oncology
• Virology
• Nanomedicine
• Immunology

Background:

• Oncolytic viruses (OVs) show promise in cancer treatment by selectively destroying cancer cells and stimulating anti-tumor immunity.
• Clinical application of OVs is limited by rapid clearance from the bloodstream after intravenous administration.
• Nanomedicine offers a potential solution for packaging and delivering OVs effectively.

Purpose of the Study:

• To encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes for targeted delivery.
• To leverage the recruitment of circulating monocytes expressing CCR2 into tumors for enhanced OV delivery.
• To evaluate the efficacy and safety of this nanomedicine approach in a preclinical prostate cancer model.

Main Methods:

• Oncolytic adenovirus (Ad[I/PPT-E1A]) was encapsulated into liposomes coated with CCL2.
• The uptake of liposome-encapsulated OVs by CCR2-expressing monocytes was assessed.
• In vitro oncolytic activity and toxicity were evaluated using prostate tumor cells.
• In vivo efficacy was tested in prostate cancer-bearing mice following intravenous administration.

Main Results:

• Successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes was achieved.
• Liposomes were preferentially taken up by CCR2-expressing monocytes.
• Encapsulation did not compromise the in vitro oncolytic activity of the virus and showed no toxicity.
• Intravenous administration significantly reduced tumor size and pulmonary metastasis in mice, requiring 1000-fold less virus compared to free OVs.

Conclusions:

• CCL2-coated liposomes effectively deliver oncolytic adenovirus to monocytes, enhancing tumor targeting.
• This liposome-assisted nanomedicine approach significantly improves the therapeutic efficacy of OVs against prostate cancer in vivo.
• The strategy holds promise for overcoming delivery challenges and improving the clinical applicability of oncolytic virus therapy for inaccessible tumors.