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| Status |
Public on Aug 06, 2019 |
| Title |
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] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| 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.
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| Contributor(s) |
Aoki H, Ueha S, Shitara K, Shichino S, Ogiwara H, Nakatsura T, Suzuki T, Shimomura M, Yoshikawa T, Shoda K, Kitano S, Yamashita M, Nakayama T, Sato A, Kuroda S, Wakabayashi M, Nomura S, Yokochi S, Ito S, Matsushima K, Doi T |
| Citation(s) |
31340866 |
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| Submission date |
Sep 18, 2018 |
| Last update date |
Aug 06, 2019 |
| Contact name |
Shigeyuki Shichino |
| E-mail(s) |
s_shichino@rs.tus.ac.jp
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| Organization name |
Tokyo University of Science
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| Department |
Department of Molecular regulation of Inflammatory and Immune Diseases
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| Street address |
2641, Yamasaki, Noda-shi
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| City |
Chiba |
| ZIP/Postal code |
278-0022 |
| Country |
Japan |
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| Platforms (2) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
| GPL23934 |
Ion Torrent S5 (Homo sapiens) |
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| Samples (105)
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| This SubSeries is part of SuperSeries: |
| GSE120102 |
TCR repertoire and transcriptomic analyses of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody |
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| Relations |
| BioProject |
PRJNA491658 |
| SRA |
SRP162009 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120101_RAW.tar |
27.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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