Nanotechnology for immuno-oncology

Abstract

Although the first generation of cancer immunotherapeutics produced unprecedented improvements in clinical outcomes for individuals with cancer, novel strategies to increase treatment specificity, delivery efficiency and pharmacokinetics are still needed. In this Review, we describe the potential advantages and current limitations of nanomaterials for cancer immunotherapy and highlight rational uses of nanosystems to generate potent and durable antitumor immune responses. We close with a review of the current state of clinical development of nanomedicine for cancer immunotherapy.

Fig. 1 |. Advantages of nanomaterials for immunotherapy delivery to tumors and immune cells.

Nanomaterials have many advantages for cancer immunotherapy, including (a) modulation of physical characteristics that dictate entry into tumors through tight junctions or trancystosis, and (b) the ability to add surface ligands to target specific cells and/or control spatiotemporal therapy delivery with environment-responsive controlled release. Nanomaterials also enable (c) efficient gene modification of desired cell types and (d) have the unique capacity for interaction with external energy sources. This property enables further control over spatiotemporal drug delivery and novel mechanisms of therapy including induction of immunogenic cell death via in situ vaccination with photodynamic therapy, magnetic hyperthermia, and ionizing radiation. CAR = Chimeric antigen receptor.

Fig. 2 |. Nanomaterials for innate immune modulation.

Schematic illustrating unique methods by which nanomaterials modulate dendritic cells (DCs), macrophages, and natural killer (NK) cells, with a focus on stimulation of damage- and pathogen-associated molecular patterns such as (a) enhanced immunogenic cell death with application of external energy sources, (b) enhanced intracellular delivery of cGAS-STING agonists, (c) direct induction of phagocytosis with bispecific macrophage-engaging nanoparticles, or (d) stimulation of toll-like receptors (TLRs) and inflammasome activation with mRNA lipid nanoparticles. NP= nanoparticle. CRT= Chemoradiation. TCR=T cell receptor.

Fig. 3 |. Nanomaterials for adaptive immune modulation.

(a) Nanomaterials targeting lymphocytes in circulation can modulate T-cell function through many unique modes of action, including modification of the redox environment with 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) or inhibiting TGF-β signaling. LNP, lipid nanoparticle. (b) Nanomaterials can also enhance chimergic antigen receptor (CAR) T-cell function through unique modes of action, including cytokine-loaded “backpacks” to overcome tumor-induced immune suppression. Alternatively, nanomaterials can be used to circumvent ex vivo manufacturing processes by generating CAR cells directly in vivo. GSH, glutathione.