Immunotherapies developed in recent years show remarkable efficacy, in some patients only, and carry the risk of significant side effects ... To improve this state of affairs, researchers have developed an approach to deliver the famous antibodies therapeutically within tumors.
How to make the antibodies, supposed to restore the aggressiveness of the immune system, be very effective within the tumor and do not intervene in other sites by causing potential autoimmune reactions? The question is crucial as these new immunotherapies have proven their effectiveness, including long-term, in some patients, but can also induce complex side effects to manage in others. In this context, the targeting of antibodies to the tumor is a challenge that Chinese researchers have attempted to tackle, apparently successfully.
This result was obtained thanks to the design of a real logistics platform at the nanometric scale: anti-PDL1 antibodies were fixed on a matrix of molecules, some of which were sensitive to the action of a protein particularly present in the microenvironment of tumors (the MMP-2 protein). At this assembly, the researchers added green indocyanine, which produces small reactive oxygen molecules when exposed to infrared light.
When this complex nanoparticle was injected into the bloodstream, anti-PDL1 antibodies were "protected" in the molecular matrix and could not react with healthy tissue. Due to the altered properties of tumor blood vessels, whose permeability is not the same as that of other tissues, nanoparticles tended to accumulate in tumors, be they primary tumors or metastases. In tumors, the MMP-2 enzyme did its work and degraded the matrix of nanoparticles, releasing the anti-PDL1 that could finally bind to their target, expressed on the surface of tumor cells. Finally, the latest salvo prepared by the researchers: the exposure of the tumor zone to an infrared laser was used to activate the green indocyanine which then emitted oxygenated molecules. However, the reactivity of these causes damage to the surrounding cells and promotes the entry of immune cells into the tumor.
In vivo experiments conducted by Chinese researchers have confirmed the effectiveness of the nano-therapeutic platform. The results show that primary tumors, such as metastases, undergo the action of oxygen molecules and the reactivated immune system. Modulation of embedded tools could also be considered, with the use of other immune control point inhibitor antibodies, such as anti-PD1, for example.