New Method Uses Just a Drop of Blood to Monitor Lung Cancer Treatment


Source: Osaka University

Summary: A team of researchers have devised a simple method for testing the impact of nivolumab in the body. This method measures how nivolumab binds to PD-1 on T-cells weeks after treatment and could provide information needed to monitor treatment more effectively.


Dr. Tasuku Honjo won the 2018 Nobel Prize in physiology or medicine for discovering the immune T-cell protein PD-1. This discovery led to a set of anti-cancer medications called checkpoint inhibitors, one of the first of which was nivolumab (Opdivo). Nivolumab helps T-cells fight tumors, however, different patients respond in different ways. It now appears that monitoring the effect of nivolumab on critical immune cells with simple and novel methods may help guide decisions to optimize treatment. Dr. Shohei Koyama and a team of researchers from Osaka University have devised a simple method for testing the impact of nivolumab in the body. This method measures how nivolumab binds to PD-1 on T-cells weeks after treatment and could provide information needed to monitor treatment more effectively. The study findings were published in the journal JCI Insight.

Opdivo

Binding status of Nivolumab can be divided into three different types based on occupancy of PD-1 in T cells: complete binding, partial binding and no binding. PD-L1 can interact with T cells already in partial binding status. Credit: Osaka University

The researchers analyzed tiny samples of blood and lung fluid from patients with lung cancer. They measured the amount of nivolumab bound to T-cells, and they also isolated only those T-cells bound by nivolumab to comprehensively analyze cell activation. The researchers found that the effects of nivolumab on T-cells often persisted in patients for a considerable time after dosing. Their findings also confirmed that the level of T-cell binding does not indicate the functional effect of the drug. A further measure of T-cell proliferation is needed. Results from two study participants illustrate the importance of measuring both proliferation and T-cell binding. The first patient showed no response when proliferation was low. In contrast, the second patient showed no tumor growth when proliferation was higher.

Co-author Takeshi Uenami said, “Our combination strategy of monitoring nivolumab binding and the proliferation status of T-cells, is a better way to determine the effect of this drug than monitoring the blood level of nivolumab alone.”


More Information: Akio Osa et al, “Clinical implications of monitoring nivolumab immunokinetics in non–small cell lung cancer patients”, JCI Insight (2018). DOI: 10.1172/jci.insight.59125 


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