The era of bioengineering: how will this affect the next generation of cancer immunotherapy?

Abstract

BackgroundImmunotherapy consists of activating the patient’s immune system to fight cancer and has the great potential of preventing future relapses thanks to immunological memory. A great variety of strategies have emerged to harness the immune system against tumors, from the administration of immunomodulatory agents that activate immune cells, to therapeutic vaccines or infusion of previously activated cancer-specific T cells. However, despite great recent progress many difficulties still remain, which prevent the widespread use of immunotherapy. Some of these limitations include: systemic toxicity, weak immune cellular responses or persistence over time and most ultimately costly and time-consuming procedures.Main bodySynthetic and natural biomaterials hold great potential to address these hurdles providing biocompatible systems capable of targeted local delivery, co-delivery, and controlled and/or sustained release. In this review we discuss some of the bioengineered solutions and approaches developed so far and how biomaterials can be further implemented to help and shape the future of cancer immunotherapy.ConclusionThe bioengineering strategies here presented constitute a powerful toolkit to develop safe and successful novel cancer immunotherapies.

Immunostimulatory biomaterials to boost tumor immunogenicity

“…Due to the systemic administration of nanoparticles, they are able to interact with a wide range of targets and elicit multifaceted immune responses. 74,97,98 That said, nanoparticles face a myriad of systemic and cellular trafficking barriers, particularly depending upon the type of drug (e.g. small molecule, antibody, nucleic acid) and final destination.…”

Biomaterial-Based Activation and Expansion of Tumor-Specific T Cells

“…Biomaterials have proven valuable in reducing systemic toxicities, enhancing accumulation in tumors, improving pharmacokinetics and ensuring sustained release by controlled (targeted) drug delivery (12, 13). Biomaterial-based immunotherapeutic strategies led to the development of nanoparticles for the targeted delivery of cargo to immune cells in vivo , such as cytokines, DC-activating agents or small inhibitors (13–15). Careful design can be applied to tune the delivery of DC-targeted vaccines using materials responsive to temperature (16) or pH (17, 18).…”

Immunostimulation and Immunosuppression: Nanotechnology on the Brink

“…Another approach that combines the delivery of anticancer drugs and immunomodulating agents consists of a "two-hit" strike to cancer cells: firstly, the cytotoxic effect of the drug leads to the cell apoptosis and activation of APCs that triggers an immune response, and secondly, the action of an immunomodulating agent improves and sustains such immune response ( Figure 11B). [168] As an example, Heo et al evaluated the sequential administration of a chemotherapeutic agent (paclitaxel), followed by PLGA nanoparticles containing the adjuvant (CPG OND) as a strategy for chemoimmunotherapy. [169] The tumor-associated antigens were generated after the primary injection with a polymer-paclitaxel complex, and these antigens were taken up by the tumor-recruited DCs.…”