Figure 2. Integration of nanotechnology and immuno-oncology for cancer therapy.

(A) For in situ cancer vaccine: Intravenously or peritumorally injected nanoparticles induce tumor cell necrosis and actuate antigen release, then the antigens are captured by nanoparticles and delivered to the tumor-draining lymph nodes, where antigens are presented, and antigen-presenting cells mature and prime T cells. Then the activated T cells infiltrate into the tumor and kill tumor cells. Activated T cells can also systematically distribute and eliminate distal tumors or metastases. (B) For checkpoint inhibitor therapy: Nanoparticles loaded with genes encoding protein therapeutics can be delivered for local production of cytokines, immune checkpoint antibodies or other protein therapeutics including BiTE. (C) For ACT therapy: Nanotechnology can be integrated with CAR-T cells and facilitate construction of ‘armed’ CAR-T cells by multiplexing with necessary cytokines and immunomodulators. This process can be realized either ex vivo or in vivo to minimize ex vivo engineering workflow. (D) For BsAb therapy: Nanotechnology can be integrated with BiTE for construction of mfBiNE, leveraging the unique properties like flexible surface decoration and cargo loading ability of nanoparticles. mfBiNE holds the advantages of long circulation, multivalent or multi-type decoration, as well as loading with supporting drugs to augment the capability of killer cells against solid tumors, which is so far unachievable. Figures created with BioRender.com. Abbreviations: ACT, adoptive cell transfer; CAR, chimeric antigen receptor; BiTE, bi-specific T cell engager; mfBiNE, multifunctional bispecific nano-engager.