The NanoLymph: Implantable. Adaptable. Anti-Cancer.

Led by Alessandro Grattoni, PhD, Professor of Nanomedicine and Corrine Chua, Ph.D., Assistant Professor, Houston Methodist researchers developed an implantable cancer vaccine device called “NanoLymph” that can recruit and activate antitumor immune cells locally to elicit a systemic antitumor immune response. The device would be implanted subcutaneously and consists of a dual reservoir to hold immune stimulants and antigens. After the incision has healed and any immune response to the foreign body has resolved, the device would be loaded transcutaneously with immunostimulants and hydrogel-encapsulated antigen in the respective reservoirs. The immune stimulants would then be eluted across a nanoporous membrane into the antigen chamber forming a drug-antigen gradient within the device, which would trigger local recruitment of DCs. DCs would then interact with the encapsulated antigens in the device then head to local lymph nodes to generate a sustained systemic antitumor T cell response. Unlike other cancer vaccine approaches, NanoLymph is designed to be a long-term platform that can be refilled with minimal invasiveness to provide continued immune activation that can be tailored based on a patient’s ongoing response to the therapy. Sustained and continual elution of drugs and antigens allows the NanoLymph to generate an enriched local microenvironment that is conducive to DC localization, activation and cross-presentation to T cells across the lymph system. In addition, the authors demonstrate that the NanoLymph is biocompatible, mechanically stable and minimally invasive, making it ideal for future clinical translation. Because of its considerable flexibility, the NanoLymph could also be utilized to effectively manage other diseases modulated by the immune system. For example, the NanoLymph could be leveraged for allergy immunotherapy to desensitize patients against common life-threatening allergens. Specifically, the NanoLymph could be used to elute cytokines or mTOR inhibitors, with house dust mite allergoid as the antigen. In this context, the NanoLymph could induce allergen desensitization by tolerogenic DCs (immuno-suppressive dendritic cells) suppressing Th2-mediated immune responses. Most available medical implants cannot be refilled and rely on either complete structure degradation or removal and reimplantation, posing a significant barrier to providing continued care. With this publication, Grattoni and his team present a proof-of-concept study demonstrating that drug and antigen locally released from the NanoLymph in a spatiotemporal manner successfully recruits and activates DCs to induce an antigen-specific antitumor immune response. Future studies will evaluate the prophylactic and therapeutic efficacy of the antitumor immune response for cancer treatment. This work lays the foundation for development of an immunomodulatory niche that could significantly improve success of cancer immunotherapy and is also adaptable for multiple disease etiologies.