Making Lung Cancer Immunotherapy More Personal

Patient responses could be better assessed by monitoring nivolumab binding to T-cells as well as the proliferation status of T-cells, researchers say.

AsianScientist (Oct. 26, 2018) – A team of scientists in Japan has devised a method to better measure the efficacy of the cancer immunotherapy nivolumab. Their findings are published in JCI Insight.

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. Nivolumab helps T-cells fight tumors.

However, different patients respond in different ways to nivolumab treatment. Monitoring the effect of nivolumab on critical immune cells with simple and novel methods may help guide decisions to optimize treatment.

In the present study, Dr. Shohei Koyama and a team of researchers from Osaka University, Japan, have devised a straightforward 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 researchers analyzed small-volume samples of blood and lung fluid from patients with lung cancer. They measured the amount of nivolumab bound to T-cells and 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.

“Our simplified method was feasible in real-world patients and demonstrated that nivolumab binds T-cells for more than 20 weeks even after the patient has stopped treatment,” said study co-author Professor Atsushi Kumanogoh of Osaka University. “Also, the plasma concentration at which nivolumab stops binding T-cells, and the percentage of bound T-cells, varies from patient to patient.”

Their findings also confirmed that the level of T-cell binding does not indicate the functional effect of the drug, and that a further measure of T-cell proliferation is needed. Results from two study participants further illustrated the importance of measuring both proliferation and T-cell binding. The first patient showed no response when T-cell proliferation was low. In contrast, the second patient showed no tumor growth when T-cell proliferation was higher.

“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,” said co-author Dr. Takeshi Uenami of Osaka University.

A better understanding of the persisting effects of nivolumab in patients may also be useful for preventing treatment-related side effects and guiding the selection of additional therapies.

The article can be found at: Osa et al. (2018) Clinical Implications of Monitoring Nivolumab Immunokinetics in Non–small Cell Lung Cancer Patients.


Source: Osaka University; Photo: Shutterstock.
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