Details

Autor(en) / Beteiligte

• Creelan, Benjamin C.
• Wang, Chao
• Teer, Jamie K.
• Toloza, Eric M.
• Yao, Jiqiang
• Kim, Sungjune
• Landin, Ana M.
• Mullinax, John E.
• Saller, James J.
• Saltos, Andreas N.
• Noyes, David R.
• Montoya, Leighann B.
• Curry, Wesley
• Pilon-Thomas, Shari A.
• Chiappori, Alberto A.
• Tanvetyanon, Tawee
• Kaye, Frederic J.
• Thompson, Zachary J.
• Yoder, Sean J.
• Fang, Bin
• Koomen, John M.
• Sarnaik, Amod A.
• Chen, Dung-Tsa
• Conejo-Garcia, Jose R.
• Haura, Eric B.
• Antonia, Scott J.

Titel

Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial

Ist Teil von

• Nature medicine, 2021-08, Vol.27 (8), p.1410-1418

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3–29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer. Adoptive cell therapy with tumor-infiltrating lymphocytes in metastatic lung cancer patients is safe and elicits antitumor activity, including ongoing complete responses, in association with polyclonal T cell responses against tumor antigens.