Neoantigen-Specific CD8+ T cell Therapy in Patients with Advanced Solid Tumors

Currently, the optimal lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8+ T cell (Neo-T) therapy has yet to be determined. We report a phase 1 study (NCT02959905) of Neo-T therapy with lymphodepletion at various dose intensity in patients with locally advanced or metastatic melanoma and colon cancers that are refractory to standard therapies. The primary end point is safety and the secondary end point is objective response rate (ORR). Results show that the treatment is well tolerated with lymphopenia being the most common adverse event in the highest-intensity lymphodepletion groups. Neo-T infusion-related adverse events are only grade 1-2 in the no lymphodepletion group. The median progression-free survival is 7.1 months (95% CI:3.7-9.8), the median overall survival is 16.8 months (95% CI: 11.9-31.7), and the ORR is 33.3% (3/9) among all groups. Three patients achieve partial response, two of them are in the no lymphodepletion group. One of the partial response patients refractory to prior anti-PD-1 therapy also respond to Neo-T therapy in the group without lymphodepletion pretreatment. Neoantigen specific TCRs are examined in two patients and show delayed expansion after lymphodepletion treatment. In summary, Neo-T therapy without lymphodepletion could be a safe and promising regimen for advanced solid tumors.