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.

American Association for the Advancement of Science