Melanoma Checkpoint Therapy More Potent in Combination with Nanovaccine

Source: GEN NEWS, September 2019

Dissonant signaling, which can deafen the immune system to cancer, can be replaced by something more harmonious—and therapeutic—if immunotherapies silence a note, sound another, or play an especially resonant chord. This last approach was taken by researchers based at Tel Aviv University (TAU) when they decided to score a requiem for melanoma, the most aggressive type of skin cancer.

Performing in vitro and animal studies, the TAU scientists combined several forms of immunotherapy, reaching a most effective crescendo when they added a nanovaccine—a particle made of biodegradable polymer, sized at 160–190 nanometers, and packed with tumor-associated antigens. Actually, two nanovaccines were evaluated. One was studded with mannose receptors and capable of ligand-mediated (active) targeting of dendritic cells. The other was mannose free and capable only of phagocytosis-dependent (passive) targeting.

When the mannosylated nanovaccines were combined with an anti-PD-1 antibody (?PD-1) for immunosuppression blockade and an anti-OX40 antibody (?OX40) for effector T-cell stimulation, expansion, and survival, robust and widespread complementary outcomes against melanoma were achieved. Details of this work appeared August 5 in the journal Nature Nanotechnology, in an article titled, “Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators.”