دورية أكاديمية
CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.
| العنوان: | CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. |
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| المؤلفون: | Pal SK; Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California., Tran B; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Haanen JBAG; Netherlands Cancer Institute, Amsterdam, the Netherlands.; Leiden University Medical Center, Leiden, the Netherlands.; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Hurwitz ME; Yale School of Medicine, New Haven, Connecticut., Sacher A; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Departments of Medicine and Immunology, University of Toronto, Toronto, Canada., Tannir NM; University of Texas MD Anderson Cancer Center, Houston, Texas., Budde LE; Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California., Harrison SJ; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Klobuch S; Netherlands Cancer Institute, Amsterdam, the Netherlands., Patel SS; Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Meza L; Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California., Dequeant ML; CRISPR Therapeutics, Boston, Massachusetts., Ma A; CRISPR Therapeutics, Boston, Massachusetts., He QA; CRISPR Therapeutics, Boston, Massachusetts., Williams LM; CRISPR Therapeutics, Boston, Massachusetts., Keegan A; CRISPR Therapeutics, Boston, Massachusetts., Gurary EB; Formerly employed by CRISPR Therapeutics, Boston, Massachusetts., Dar H; CRISPR Therapeutics, Boston, Massachusetts., Karnik S; CRISPR Therapeutics, Boston, Massachusetts., Guo C; Formerly employed by CRISPR Therapeutics, Boston, Massachusetts., Heath H; CRISPR Therapeutics, Boston, Massachusetts., Yuen RR; CRISPR Therapeutics, Boston, Massachusetts., Morrow PK; Formerly employed by CRISPR Therapeutics, Boston, Massachusetts., Agarwal N; Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Srour SA; University of Texas MD Anderson Cancer Center, Houston, Texas. |
| المصدر: | Cancer discovery [Cancer Discov] 2024 Jul 01; Vol. 14 (7), pp. 1176-1189. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase I; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
| مواضيع طبية MeSH: | Carcinoma, Renal Cell*/therapy , Carcinoma, Renal Cell*/immunology , Kidney Neoplasms*/therapy , Kidney Neoplasms*/immunology , Immunotherapy, Adoptive*/methods , CD27 Ligand*, Humans ; Animals ; Mice ; Female ; Male ; Middle Aged ; Receptors, Chimeric Antigen/immunology ; Aged ; Xenograft Model Antitumor Assays ; Cell Line, Tumor ; Adult |
| مستخلص: | Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70- targeted allogeneic CAR T cells. Significance: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors. (©2024 The Authors; Published by the American Association for Cancer Research.) |
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| المشرفين على المادة: | 0 (CD27 Ligand) 0 (Receptors, Chimeric Antigen) 0 (CD70 protein, human) |
| تواريخ الأحداث: | Date Created: 20240407 Date Completed: 20240701 Latest Revision: 20240703 |
| رمز التحديث: | 20240703 |
| مُعرف محوري في PubMed: | PMC11215406 |
| DOI: | 10.1158/2159-8290.CD-24-0102 |
| PMID: | 38583184 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2159-8290 |
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| DOI: | 10.1158/2159-8290.CD-24-0102 |