Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Journal for immunotherapy of cancer - 12(2024), 2 vom: 05. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Botta, Gregory P [VerfasserIn] |
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| Links: |
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| Themen: |
Antigens, CD19 |
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| Anmerkungen: |
Date Completed 07.02.2024 Date Revised 14.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/jitc-2023-007927 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368057828 |
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| 245 | 1 | 0 | |a Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells |
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| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gastrointestinal Neoplasms | |
| 650 | 4 | |a Receptors, Chimeric Antigen | |
| 650 | 4 | |a Therapies, Investigational | |
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| 700 | 1 | |a Ma, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Hahn, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Sierra, Gloria |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Hendrix, Amanda Y |e verfasserin |4 aut | |
| 700 | 1 | |a Nolte Fong, Joy V |e verfasserin |4 aut | |
| 700 | 1 | |a Ween, Audrey |e verfasserin |4 aut | |
| 700 | 1 | |a Vu, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Aaron |e verfasserin |4 aut | |
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| 700 | 1 | |a Jamieson, Catriona |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zonghai |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Ezra |e verfasserin |4 aut | |
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