In Situ Vaccine Uses Immune Response to Treat Cancer

Antagonistic anti-OX40 antibody triggers T-cell immune response specific to tumor antigens

lab mouse

WEDNESDAY, Jan. 31, 2018 (HealthDay News) -- In situ vaccination is an approach that can trigger an immune response in a manner that is specific to the tumor antigens to treat malignancy, according to a study published online Jan. 31 in Science Translational Medicine.

Idit Sagiv-Barfi, Ph.D., from Stanford University in California, and colleagues used a noncustomized approach called in situ vaccination to treat malignancy. Immune-enhancing agents were injected locally into one tumor site in mice, which triggered a T-cell immune response locally that went on to attack cancer throughout the body. A screening strategy was used in which the same syngeneic tumor was implanted at two distinct sites in the body. The test agent was injected into one tumor, and the resulting immune response was detected by regression of the distant tumor.

The researchers found that the most impressive results were seen for the combination of unmethylated CG-enriched oligodeoxynucleotide (CpG) -- a Toll-like receptor 9 (TLR9) ligand -- and anti-OX40 antibody. TLRs recognize molecular patterns on pathogens as part of the innate immune system. In mouse or human tumors, low doses of CpG injected into a tumor induced expression of OX40 on CD4+ T cells in the microenvironment. An agonistic anti-OX40 antibody triggered a T-cell immune response that was specific to the injected tumor antigens.

"Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers," the authors write.

One author is founder and equity holder of CellSight, which develops and translates multimodality strategies for imaging cell trafficking/transplantation.

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