Immunotheranostic microbubbles (iMBs) - a modular platform for dendritic cell vaccine delivery applied to breast cancer immunotherapy

Abstract

Background: Therapeutic strategies engaging the immune system against malignant cells have revolutionized the field of oncology. Proficiency of dendritic cells (DCs) for antigen presentation and immune response has spurred interest on DC-based vaccines for anti-cancer therapy. However, despite favorable safety profiles in patients, current DC-vaccines have not yet presented significant outcome due to technical barriers in active DC delivery, tumor progression, and immune dysfunction. To maximize the therapeutic response, we present here a unique cell-free DC-based vaccine capable of lymphoid organ targeting and eliciting T-cell-mediated anti-tumor effect. Methods: We developed this novel immunotheranostic platform using plasma membranes derived from activated DCs incorporated into ultrasound contrast microbubbles (MBs), thereby offering real-time visualization of MBs’ trafficking and homing in vivo. Human PBMC-derived DCs were cultured ex vivo for controlled maturation and activation using cell membrane antigens from breast cancer cells. Following DC membrane isolation, immunotheranostic microbubbles, called DC-iMBs, were formed for triple negative breast cancer treatment in a mouse model harboring a human reconstituted immune system. Results: Our results demonstrated that DC-iMBs can accumulate in lymphoid organs and induce anti-tumor immune response, which significantly reduced tumor growth via apoptosis while increasing survival length of the treated animals. The phenotypic changes in immune cell populations upon DC-iMBs delivery further confirmed the T-cell-mediated anti-tumor effect. Conclusion: These early findings strongly support the potential of DC-iMBs as a novel immunotherapeutic cell-free vaccine for anti-cancer therapy.