Opdivo trial provides new insights into how immuno-oncology drugs can be enhanced

Despite the success of checkpoint inhibitors that remove the blockade that cancer cells impose on the immune system, the drugs only work in some patients. A research team led by scientists from the University of California, Los Angeles, understood how immune cells of responders function differently from non-astonishing ones, pointing to new ways to increase the efficacy of immuno-oncology therapies. Can do.

In a new study published in Cancer Cells, the UCLA team pointed out two main drivers that help the immune system attack cancer in response to IO treatment: infiltration of T-cell tumors and interferon-gamma signaling.

Researchers analyzed tumor biopsies from melanoma patients treated with Bristol Myers Squibb’s PD-1 inhibitor Opdivo in either Checkmate-2010 trial with the company’s anti-CTLA-4 drug Yervoy. They compared genomic data from tumors collected before and after treatment in both patients who had a clinical response and those who did not respond.

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As reported by previous researchers, UCLA scientists found that high levels of CD8 T cells traveling to the tumor were associated with clinical response to checkpoint inhibitors.

So, they investigated the expression of cancer cell-killing cytokines as a result of tumor antigen-specific T-cell activation. The team found that cytokine expression followed a pattern of interferon-gamma, which was found at higher levels in biopsies of patients who responded well to checkpoint inhibitors.

Further analysis of genes related to interferon-gamma exposure revealed that the isolates of the main patients, who responded and those who resisted IO therapy, had increased antigen-presenting machinery.

The study’s senior author, Antony Ribas, MD, PhD, stated in a statement, “Cancer is blocking how the immune system attacks cancer cells by immune cells.” “And whenever we release them, there’s an enhanced immune activation that depends on the strength of T cells to produce [interferon gamma]As a result of the activation of more than 600 genes, which enhance the antitumor immune response. ”

Related: New Insights into Cancer Cell Escape Mechanisms May Promote Immuno-Oncology Treatment

Several research efforts have focused on identifying ways to promote the efficacy of immuno-oncology therapies. These include targeting immune checkpoints. For example, Roach recently demonstrated that combining his PD-L1 blocker Tecentriq with the experimental anti-TIGIT antibody tiragolumab showed non-small lung cancer to be superior to only Tecentriq.

Researchers in China recently found that inhibiting AKT with Merck’s MK-2206 promoted T-cell infiltration into glioblastoma in mice. They argued that mixing the drug with an anti-PD-1 drug could improve the anti-tumor effect.

The findings of the UCLA-led team expect combination therapy to “initiate an anti-tumor immune response to increase interferon signaling inside the tumor when it is not already present”, the efficacy of immune investigator editors So that they can help more patients, scientists wrote in the study.