Scheme 1

Personalized DC-iMB strategy for TNBC immunotherapy. a Schematic illustration of DC-iMB showing the presence of synthetic phospholipids, DC membrane phospholipids and proteins, and gas core. b By nature, DC-iMB allows US imaging (e.g., tumor size and perfusion monitoring, spleen retention visualization), and targeted immunotherapy via TNBC specific antigen presentation and naïve T-cell activation in lymphoid organs (thymus, spleen, and lymph nodes). c DC-iMB vaccine preparation: Monocytes (CD14⁺) were isolated from patient’s peripheral blood for autologous DC generation (1a) while hPBMCs were used for human immune system reconstitution (i.e., T-cell engraftment) of immunodeficient NSG mice (1b). Immature monocyte-derived DCs (iMoDCs) were generated by culturing the isolated CD14⁺ cells with GM-CSF and IL-4 (2). Monocyte-derived DCs (MoDCs) were matured and pulsed with MDA-MB-231 cancer cell derived membrane antigens (3). The plasma membrane from MoDCs was then isolated (4) and used for DC-iMB formulation (5) before injection into a humanized mouse model of TNBC via several cycles of intravenous (i.v.) injections (6). CCM: cancer cell membrane; DCm: DC membrane; GM-CSF: granulocyte macrophage colony stimulating factor; LNs: lymph nodes; MHC: major histocompatibility complex; PLs: phospholipids; TLR: Toll-like receptor.