Tightening the tumor-targeting abilities of checkpoint blockade immunotherapy

Seeking to improve upon existing checkpoint inhibitor therapies, scientists have developed a common checkpoint inhibitor (anti-PD-L1) in a nanoparticle formulation, which were activated specifically at tumor sites in mouse models of cancer. Their approach intends to prevent the immune system from becoming tolerant of tumors - which occurs in 30% of all cancer patients - and could help avoid the toxic off-target effects observed during the use of standard antibody checkpoint inhibitors. As well, the antibodies used to target immune system-suppressing proteins like PD-1 and PD-L1 can fail to reach deep-seated or metastatic tumors, further hindering their efficacy. Seeking a method to overcome these hurdles, Dangge Wang and colleagues developed highly tumor-specific nanoparticles carrying PD-L1-targeting antibodies and a photosensitizer, a light-activated molecule that produces tumor-killing reactive oxygen species after encountering matrix metalloproteinase protein 2 (MMP-2), a protein abundant in tumors. In mouse models, the dual administration of PD-L1-carrying nanoparticles in conjunction with local near-infrared radiation (that activates the photosensitizer) promoted the infiltration of cancer cell-killing T cells into the tumor site and further sensitized the tumors to PD-L1 checkpoint blockade. This combination also helped the nanoparticles effectively suppress tumor growth and metastasis to the lung and lymph nodes, resulting in approximately 80% mouse survival over 70 days, compared to complete mouse death in 45 days in the group treated with only PD-L1 antibodies. With further improvement, the platform used here could be readily adapted to other immune checkpoint inhibitors for improved checkpoint blockade immunotherapy, the authors say.

Credit: 
American Association for the Advancement of Science