CELL INTELLIGENCE · 肿瘤细胞治疗研究

Patients with ovarian cancer (OC) have not yet benefitted from the advances in immuno-oncology. While tumor infiltrating lymphocytes (TILs) can be expanded from OC tumors, previous trials have not demonstrated lasting responses. High expression of the immune checkpoints PD-1 and LAG-3 on TILs from OC provide a rationale for the addition of immune checkpoint inhibitors (ICI) to the treatment. In this clinical pilot study (NCT04611126), five patients with platinum-resistant recurrent OC were treated with TIL therapy and up to four cycles of combined treatment with PD-1-/LAG-3-inhibitors. The primary endpoint was safety and feasibility, while secondary endpoints included immune monitoring and clinical efficacy.

Included patients had undifferentiated carcinoma (n = 1), high-grade serous OC (HGSOC) (n = 2) and low-grade serous OC (LGSOC) (n = 2). The treatment was safe and feasible with expected treatment-related toxicity; however, there was a relatively high rate of non-treatment-related complications.

A decrease in tumor burden was observed in 80% (4/5) of patients, including two unconfirmed partial responses. In one patient, the response was supported by in vitro reactivity of the infused TILs toward autologous tumor cell line. Differences in baseline tumor burden, infusion product composition and responses were observed in LGSOC vs. HGSOC.

Overall, this exploratory pilot study demonstrated a favorable safety profile and indications of clinical efficacy for TIL therapy combined with PD-1 and LAG-3 inhibition in platinum-resistant OC. Due to the low patient number, the results should be interpreted as hypothesis-generating, providing a rationale for conducting larger trials that carefully consider treatment timing and tumor histology.