4.1.3. Camouflage Using Cancer Cell Membranes

As previously discussed, endogenous plasma membranes from whole TCLs are a good source as antigens, mimicking the surface architecture of cancer cells and inducing interplay with immune cells by the presence of membrane-bound tumor antigens. Hence, the artificial coating of cancer cell membrane components onto NP surfaces has also been developed. Such PLGA NPs covered with cancer cell membranes (CCNPs) exhibited colloidal stability and longer circulating properties, and effectively trained the immune system to recognize and fight tumors [122]. In addition, the incorporation of cancer cell membranes onto CpG-containing NPs showed synergistic anticancer vaccination efficacy (Figure 4B) [114]. The concurrent presentation of both immunostimulatory tumor antigens and adjuvant could enhance the effective antigen presentation and the activation of downstream immune processes. Based on the facilitated expression level of co-stimulatory receptors on DCs, cancer cell membrane-associated specific antigen presentation, and higher CD8<sup>+</sup> T cell proliferation to recognize specific melanoma antigens (i.e., gp100 and TRP2), in vivo vaccination resulted in survival rates of 86% in a B16-F10 tumor model with mice.

Similarly, the combination of a mannose (Man) moiety and a TLR 7 agonist (R837) with CCNPs (Man-R837-CCNPs) showed enhanced cellular uptake and antitumor immune responses (Figure 4C) [115]. Through (1) specific binding between Man and its receptors on DCs, (2) activation of innate immunity by R837 adjuvant, and (3) stimulation by melanoma cell membranes, BMDCs treated with Man-R837-CCNPs achieved higher maturation, with the enhanced expression of CD80 and CD86 and the significantly increased secretion of cytokines (IL-12p40 and TNF-α). Although template CCNPs, R837-loaded PLGA NPs without membrane coating, and R837-CCNPs without a Man moiety slightly inhibited tumor progression compared to untreated controls in B16-OVA tumor models, Man-R837- CCNPs exhibited the strongest antitumor efficacy and vaccination through homotypic targeting mediated by cancer cell surface antigens, and increased numbers of CD8<sup>+</sup> T cells.
