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Autologous Tumor-Infiltrating Lymphocyte Treatment Under Study in Metastatic NSCLC

By: Julia Fiederlein
Posted: Tuesday, September 7, 2021

Cell therapy with autologous tumor-infiltrating lymphocytes seemed to be safe and clinically active in patients with anti–PD-1–resistant metastatic non–small cell lung cancer (NSCLC), according to a proof-of-concept phase I trial published in Nature Medicine. Scott J. Antonia, MD, PhD, of Duke University School of Medicine, Durham, North Carolina, and colleagues noted this immunotherapy approach might constitute a new treatment strategy.

“We observed that lymphocytes could be successfully expanded from most patients’ tumors and were largely capable of autologous tumor recognition,” the investigators commented. “Our report adds to growing evidence that tumor-infiltrating lymphocyte adoptive cell therapy may be active in a variety of epithelial malignancies.”

A total of 20 patients underwent excisional biopsy of their metastases; freshly resected tumor fragments were minced, and autologous tumor-infiltrating lymphocytes were expanded in a medium containing interleukin-2 (IL-2). If there was evidence of disease progression after four cycles of nivolumab therapy (n = 16), the patients underwent infusion of tumor-infiltrating lymphocytes combined with lymphodepletion chemotherapy and IL-2. Subsequently, maintenance therapy with nivolumab was administered for up to 1 year.

The final severe toxicity rate (primary endpoint: defined as ≤ 17%) was 12.5%. Of the 13 evaluable patients, 3 had confirmed responses, and 11 experienced a reduction in tumor burden. Two patients achieved complete responses; after 1.5 years, these responses were ongoing. Based on exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after tumor-infiltrating lymphocyte treatment; they seemed to be enriched in responding patients. In addition, the number of neoantigen-reactive T-cell clonotypes appeared to increase and persist in the peripheral blood after treatment.

“Based on its activity and safety profile, tumor-infiltrating lymphocytes are a rational therapy to further investigate for fit, motivated patients with metastatic NSCLC,” the authors concluded. “Larger trials are required to further define the optimal biomarkers of response….”

Disclosure: For full disclosures of the study authors, visit nature.com.



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