Research press release


Nature Medicine

Medical research: Combined immunotherapy to treat metastatic lung cancer assessed



B Creelanたちは、ニボルマブという薬を使った免疫チェックポイント阻害療法とTILとの組み合わせが転移性肺がんの治療にどのように役立つかを、20人の患者コホートで第1相臨床試験を行って調べた。治療を行ってから数週間以内に、複数の患者で臨床活性の兆候が見られるようになり、2人の患者では腫瘍が寛解した。TILの分子解析や腫瘍生検検体の塩基配列解読が行われ、ほとんどの患者で観察された治療応答は、腫瘍細胞が発現する抗原のTILによる認識と関連していることが確かめられた。一部の症例では、このような抗原に特異性を示すTILは、その抗腫瘍活性を1年以上も維持していた。TILとニボルマブの併用は、今後が期待できる有効性を示しただけでなく、副作用はあるが対処が可能で、安全であると見なされた。


Combining two types of immunotherapy — immune-checkpoint inhibition and adoptive cell therapy using tumor-infiltrating lymphocytes — elicits anti-tumor responses in patients with metastatic lung cancer, according to a paper published in Nature Medicine. These proof-of-concept data (involving 20 participants) may offer a new treatment approach for patients with advanced lung cancer.

Immune-checkpoint inhibition — a type of immunotherapy in which drugs are administered to inhibit protein regulators of the immune system — produces clinical responses in only a subset of patients with cancer. Recently, there has been increasing interest in the use of autologous tumor-infiltrating lymphocytes (TILs) as a therapeutic approach for cancer treatment, notably in the case of breast and melanoma skin cancers. This strategy involves harvesting immune cells called ‘T cells’ from a patient’s tumors, co-culturing them in the laboratory with tumor cells, expanding those that exhibit reactivity against cancer cells, and re-introducing them into patients.

Benjamin Creelan and colleagues conducted a phase 1 clinical trial investigating how immune-checkpoint inhibition therapy using the drug nivolumab could be combined with the TILs to treat metastatic lung cancer in a cohort of 20 patients. Within a few weeks of treatment, several patients were found to display signs of clinical activity, with two patients achieving remission of their tumors. By conducting a molecular analysis of TILs and genetically sequencing tumor biopsies, the authors confirmed that the responses observed in most patients were associated with TILs’ recognizing antigens expressed by tumor cells. In some cases, TILs specific to these antigens maintained their anti-tumor activity for over a year. Not only did the combination of TILs with nivolumab display promising efficacy, but it was also considered safe, with manageable adverse effects.

Although this pilot trial was performed with a small number of patients, the authors conclude that this combinative therapy might constitute a promising new treatment strategy for advanced forms of this disease.

doi: 10.1038/s41591-021-01462-y


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