Data from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes

• DOI: 10.1158/2326-6066.c.7311380.v1
• Publication Date: 2024-07-02T09:31:50Z
• Authors: David König; Michael T. Sandho...; Sarp Uzun; Andreas Zingg; Reto Ritschard; Helen Thut; Katharina Glatz; Elisabeth A. Kappos; Dirk J. Schaefer; Christoph Kettelhack; Jakob R. Passweg; Andreas Holbro; Katharina Baur; Michael Medinger; Andreas Buser; Didier Lardinois; Lukas T. Jeker; Nina Khanna; Frank Stenner; Benjamin Kasenda; Krisztian Homicsko; Matthias Matter; Natalia Rodrigues...; Alfred Zippelius; Heinz Läubli

<div>Abstract<p>Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance to TIL-ACT possibly due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To the best our knowledge, this is the first case of clonal selection of a pre-existing nondominant tumor cell clone; this report demonstrates the mechanism involved in secondary resistance to TIL-ACT that can potentially change current clinical practice because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before treatment with TIL-ACT.</p></div>