GSE120101
T-cell receptor repertoire analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [TCR-seq]
Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed cell death-1 monoclonal antibodies (mAbs) agents or these combinations has improved outcomes of various cancers.However, still not a few patients fail to achieve clinical benefit, this highlights the importance of additional treatment to overcome its resistance. Previously, we showed that administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs in B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models. IT1208 (IDAC Theranostics, Tokyo, Japan) is a humanized anti-CD4 immunoglobulin G1 (IgG1) monoclonal antibody with a defucosylated Fc region, which markedly enhances antibody dependent cellular cytotoxicity. In a first-in-human, phase I, open-label, dose-escalation study, we performed T cell repertoire analysis of T cell subsets in the tumors and peripheral blood mononuclear cells (PBMCs) to clarify T cell responses against IT1208 monotherapy in patients with advanced solid tumors. Overall design: Four and seven patients were assigned to dose levels 1 (0.1mg/kg) and 2 (1.0 mg/kg), having gastrointestinal cancer. First patient in each cohort was treated as one dose of IT1208 on day 1 and other patients received two doses of IT1208 on day 1 and 8. To clarify T cell repertoire changes by IT1208 monotherapy, PBMC collection and tumor biopsy were conducted before the study treatment and just after dose-limiting toxicities evaluation period whenever possible. Then, we performed T cell receptor (TCR)-seq analysis by using Ion Proton or Ion Genestudio S5 sequencers.