Evaluating the safety and efficacy of CRISPR/AaCas12b Max -modified tumor infiltrating lymphocytes (GT300) as monotherapy in advanced solid tumors.

作者：Pin Wang, Haifeng Qin, Zhengxiang Han, Jing Guo, Jing Yu, Liqing Ma, Long‐Sheng Lu, Hanyi Zhang, Yishan Liu, Jia Deng, Yarong Liu · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.5613 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Cytomegalovirus and herpesvirus research、Immune Cell Function and Interaction

5613 Background: Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) has shown promising results in melanoma patients. However, its effectiveness in other solid tumors, especially "cold" tumors, is still being explored. GT300, a next-generation TIL product, is engineered using CRISPR/AaCas12bMax to disrupt two key immunoregulatory targets identified through genome-wide CRISPR screening. This modification aims to enhance TIL function and overcome the suppressive tumor microenvironment, potentially expanding its use to cold tumors like ovarian and colorectal cancer. Therefore, two studies were initiated to assess the preliminary safety and efficacy of GT300 in advanced solid tumors. Methods: The first-in-class study aims to enroll patients with advanced, treatment-refractory solid tumors, focusing on gynecological cancers. After determining the optimal biological dose (OBD), a monotherapy expansion phase will begin for patients with various solid tumors. Participants undergo nonmyeloablative (NMA) lymphodepletion and receive an infusion of the G300 TIL product, followed by IL-2 administration. Results: As of September 5, 2024, five patients have been enrolled in these two studies, with a median age of 55 years and a median of two prior therapy lines. After FC lymphodepleting chemotherapy, patients received GT300 infusions at doses of ≥1 × 10⁹ viable cells. Four out of five patients subsequently received IL-2. Most adverse events (AEs) were Grade 1 or 2,...