Vesicular Antibodies: A Bioactive Multifunctional Combination Platform for Targeted Therapeutic Delivery and Cancer Immunotherapy

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in oncology. The use of nanovesicles (NVs) as chemotherapeutic delivery vehicles has been recently proven successful, yet monotherapy with monomodalities remains a significant limitation for solid tumor treatment. Here, as a proof of principle, a novel cell-membrane-derived NVs that can display full-length monoclonal antibodies (mAbs) is engineered. The high affinity and specificity of mAb for tumor-specific antigens allow these vesicular antibodies (VAs) to selectively deliver a cytotoxic agent to tumor cells and exert potent inhibition effects. These VAs can also regulate the tumor immune microenvironment. They can mediate antibody-dependent cellular cytotoxicity to eradicate tumor cells via recruitment and activation of natural killer cells in the tumor. Upon further encapsulation with chemotherapeutic agents, the VAs show unequaled cooperative effects in chemotherapy and immunotherapy in tumor-bearing mice. As far as it is known, this is the first report of a VA-based multifunctional combination therapy platform. This might lead to additional applications of vesicular antibodies in cancer theranostics.