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Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial
Open accessAbstract
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.
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Metadata
- Authors
- Creelan, B. C., Wang, C., Teer, J. K., Toloza, E. M., Yao, J., Kim, S., Landin, A. M., Mullinax, J. E., Saller, J. J., Saltos, A. N., Noyes, D. R., Montoya, L. B., Curry, W., Pilon-Thomas, S. A., Chiappori, A. A., Tanvetyanon, T., Kaye, F. J., Thompson, Z. J., Yoder, S. J., Fang, B., Koomen, J. M., Sarnaik, A. A., Chen, D.-T., Conejo-Garcia, J. R., Haura, E. B., & Antonia, S. J.
- Venue
- Nature Medicine
- Published
- 2021-08
- Volume
- 27
- Issue
- 8
- Pages
- 1410-1418
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3193095160
- Cited by
- 428
- References
- 57
- FWCI
- 22.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Creelan, B. C., Wang, C., Teer, J. K., Toloza, E. M., Yao, J., Kim, S., Landin, A. M., Mullinax, J. E., Saller, J. J., Saltos, A. N., Noyes, D. R., Montoya, L. B., Curry, W., Pilon-Thomas, S. A., Chiappori, A. A., Tanvetyanon, T., Kaye, F. J., Thompson, Z. J., Yoder, S. J., . . . Antonia, S. J. (2021). Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nature Medicine. https://doi.org/10.1038/s41591-021-01462-y
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
