Artificially Reprogrammed Macrophages as Tumor‐Tropic Immunosuppression‐Resistant Biologics to Realize Therapeutics Production and Immune Activation

Abstract

To engineer patient‐derived cells into therapy‐purposed biologics is a promising solution to realize personalized treatments. Without using gene‐editing technology, a live cell‐typed therapeutic is engineered for tumor treatment by artificially reprogramming macrophages with hyaluronic acid‐decorated superparamagnetic iron oxide nanoparticles (HIONs). This nanoparticle‐assisted cell‐reprogramming strategy demonstrates profound advantages, due to the combined contributions from the biological regulation of HIONs and the intrinsic nature of macrophages. Firstly, the reprogrammed macrophages present a substantial improvement in their innate capabilities, such as more effective tumor targeting and more efficient generation of bioactive components (e.g., reactive oxygen species, bioactive cytokines) to suppress tumor growth. Furthermore, this cell therapeutic exhibits cytostatic/proapoptotic effects specific to cancer cells. Secondly, HIONs enable macrophages more resistant to the intratumoral immunosuppressive environment. Thirdly, the macrophages are endowed with a strong ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine‐like manner. Consequently, a synergistic tumor‐inhibition effect is achieved. This study shows that engineering nanomaterial‐reprogrammed live cells as therapeutic biologics may be a more preferable option to the commonly used approaches where nanomaterials are administrated to induce bioresponse of certain cells in vivo.

Cellular backpacks for macrophage immunotherapy

“…S8 for hierarchical gating). An emergent therapeutic strategy to attack tumorous tissues is via repolarizing TAMs toward M1 phenotypes (34)(35)(36)(37)(38)(39). TAMs affect cancer progression in a manner that is dependent on their polarization (40)(41)(42).…”

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

“…At the same time, it was also pointed out that the accumulation of iron in the macrophages could cause the phenotypic switching since Fe 3 O 4 NPs could be internalized by macrophages and degraded to iron ions. The high concentration of intracellular iron ions activate the nuclear factor kappa-B (NF-κB) signaling pathway, [30] following by the phenotype conversion. In addition to Fe 3 O 4 NPs, ionic iron can also polarize macrophages.…”

“…On this basis, the internalization of iron by the macrophages after incubating with different nanomaterials was evaluated since the iron played an important role in the phenotype conversion. [30] The cytoplasm is stained red while the internalized iron is stained blue. In the PI@M group, the blue color in the cells could be clearly observed due to the effective uptake, while the blue area is hardly seen with ionic forms of iron (Figure 3e).…”

Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells

“…A cellular vaccine was generated based on the fusion between DCs and cancer cells, which offered hybrid cells that shared a unified cytoplasm but preserved the identity of dual nuclei 24,25 . It is noted that such a fused configuration induced the processing of the whole tumor antigens, including the known and the unidentified, and the immunological co-stimulatory molecules (e.g., B7 family members) on cytomembranes 26,27 . In addition, the fused cells (FCs) acquire the enhanced lymph node homing capability 28 , favoring antigen presentation to T cells in lymph nodes.…”