Researchers working on viral immunotherapy for cancer have uncovered an unexpectedly beneficial mechanism:
The study evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected directly into one of two melanoma tumors implanted in mice, followed by an antibody that essentially releases the brakes on the immune response. The researchers report that the combination induced a potent and systemically effective anti-tumor immune response that destroyed the non-infected tumor as well. Even tumor types that have hitherto proved resistant to checkpoint blockade and other immunotherapeutic strategies were susceptible to this combined therapy.
[Researchers] found that an inflammatory immune response induced in the tumor by NDV primarily accounts for the efficacy of the therapy. The checkpoint blockade antibody used in this study binds CTLA-4, a molecule found on immune cells that acts like a brake (or "checkpoint") on the immune response. A version of this antibody is already used for cancer therapy, and it has proved potent in a clinical trial evaluating its combination with another immunotherapy as well. The researchers noticed that when NDV was injected into a tumor implanted in mice, cancer-killing immune cells flooded into that tumor. "But we also found, to our surprise, that a similar infiltration of activated immune cells occurred in a distant tumor, one in which the virus was never detected."
The researchers show that NDV infection alerts T cells of the immune system to the presence of cancer cells, which otherwise suppress immune surveillance and attack. Subsequent injection of the anti-CTLA-4 antibody dials up the incipient anti-tumor response so dramatically that it overcomes the tumor's immune suppression and destroys both NDV-exposed tumors and unexposed tumors. And the effect appears to be durable. When the same tumors are reintroduced into treated animals, they are swiftly eliminated.