Table 1.

Characteristics of selected delivery strategies for cancer immunotherapies

Delivery technology	Classes of immunotherapy	Advantages	Limitations
In vivo nanoparticle delivery to immune cells	• Cytokines • Checkpoint inhibitors • Agonistic antibodies • Engineered T cells	• Surface functionalization with targeting agents • Localized delivery • Cargo protection	• Premature drug release • Nanoparticle stability • Delivery to off-target clearance organs • Systemic toxicity
Ex vivo T-cell functionalization with nanoparticles	• Cytokines • Vaccines • Engineered T cells	• Innate tumor infiltration • Improved drug delivery • Can be engineered ex vivo or in vivo	• Long production time • Short drug release profiles • Cell death after administration • Complex manufacturing
Controlled release systems	• Cytokines • Checkpoint inhibitors • Agonistic antibodies	• Extended therapy timeline • Cargo protection • Low required doses • Localized delivery following intravenous injection	• Difficult to control release profiles • Toxicities from off-target release • Potentially require surgical implantation • Acidification can degrade cargo
Biomaterial implant scaffolds	• Cytokines • Vaccines • Engineered T cells	• In situ dendritic cell activation • Delivery of dendritic cell attractants • Implant functionalization with antigen • Controlled release profiles • Provides physical structure for cells	• Potential toxicity from the implant material • Need to define specific antigens • Potential rejection of loaded adjuvant • Requires surgery
Injectable biomaterial scaffolds	• Cytokines • Checkpoint inhibitors • Neoantigens	• Minimally invasive • No surgery required • Controlled release of loaded cargo • Delivery directly to the tumor	• Early stages of development • Requires extensive characterization for biodegradation profile • May require large gauge needle
Transdermal delivery systems	• Checkpoint inhibitors • Neoantigens	• Sustained release • Low required doses • Local delivery directly to the tumor • Minimally invasive • Bio-responsive	• Small treatment area • Bioavailability and biocompatibility are unknown • Can be used only for tumors close to the skin • Complex manufacturing

Reprinted with permission from [2]