دورية أكاديمية
Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors.
| العنوان: | Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors. |
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| المؤلفون: | Lin FY; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX., Stuckert A; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX., Tat C; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX., White M; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX., Ruggieri L; Department of Neurosurgery, Baylor College of Medicine, Houston, TX., Zhang H; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Mehta B; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Lapteva N; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Mei Z; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Major A; Department of Pathology, Baylor College of Medicine, Houston, TX., Thakkar S; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Shum T; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Department of Radiology, Brigham and Women's Hospital, Boston, MA., Parikh K; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Wu MF; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Department of Medicine, Baylor College of Medicine, Houston, TX., Lindsay HB; Department of Pediatrics Heme-Onc and Bone Marrow Transplantation, Children's Hospital Colorado Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Campus, Denver, CO., Scherer L; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX., Shekar M; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX., Baxter P; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX., Wang T; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Department of Medicine, Baylor College of Medicine, Houston, TX., Grilley B; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Moeller K; Department of Radiology, Baylor College of Medicine, Houston, TX., Hicks J; Department of Pathology, Baylor College of Medicine, Houston, TX., Roy A; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Department of Pathology, Baylor College of Medicine, Houston, TX., Anastas J; Department of Neurosurgery, Baylor College of Medicine, Houston, TX., Malbari F; Department of Neurology, Baylor College of Medicine, Houston, TX., Aldave G; Department of Neurosurgery, Baylor College of Medicine, Houston, TX., Chintagumpala M; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX., Blaney S; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX., Parsons DW; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX., Brenner MK; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Department of Medicine, Baylor College of Medicine, Houston, TX., Heslop HE; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Department of Medicine, Baylor College of Medicine, Houston, TX., Rooney CM; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Omer B; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.; Dan L Duncan Comprehensive Cancer Center, Houston, TX.; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Aug 10; Vol. 42 (23), pp. 2769-2779. Date of Electronic Publication: 2024 May 21. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase I |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Receptors, Chimeric Antigen*/immunology , Receptors, Chimeric Antigen*/therapeutic use , Central Nervous System Neoplasms*/drug therapy , Central Nervous System Neoplasms*/immunology , Central Nervous System Neoplasms*/therapy , Gangliosides*/immunology, Humans ; Child ; Adolescent ; Child, Preschool ; Male ; Female ; Infant ; Young Adult ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Neoplasm Grading ; Glioma/drug therapy ; Glioma/pathology ; Glioma/therapy ; Glioma/immunology ; Interleukin-7 Receptor alpha Subunit |
| مستخلص: | Purpose: T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.CARTs). Methods: Patients age 1-21 years with H3K27-altered diffuse midline glioma (DMG) or other recurrent GD2-expressing CNS tumors were eligible for this phase I trial (ClinicalTrials.gov identifier: NCT04099797). All subjects received standard-of-care adjuvant radiation therapy or chemotherapy before study enrollment. The first treatment cohort received GD2.CARTs alone (1 × 10 7 cells/m 2 ), and subsequent cohorts received C7R-GD2.CARTs at two dose levels (1 × 10 7 cells/m 2 ; 3 × 10 7 cells/m 2 ). Standard lymphodepletion with cyclophosphamide and fludarabine was included at all dose levels. Results: Eleven patients (age 4-18 years) received therapy without dose-limiting toxicity. The GD2.CART cohort did not experience toxicity, but had disease progression after brief improvement of residual neurologic deficits (≤3 weeks). The C7R-GD2.CART cohort developed grade 1 tumor inflammation-associated neurotoxicity in seven of eight (88%) cases, controllable with anakinra. Cytokine release syndrome was observed in six of eight (75%, grade 1 in all but one patient) and associated with increased circulating IL-6 and IP-10 ( P < .05). Patients receiving C7R-GD2.CARTs experienced temporary improvement from baseline neurologic deficits (range, 2 to >12 months), and seven of eight (88%) remained eligible for additional treatment cycles (range 2-4 cycles). Partial responses by iRANO criteria were observed in two of seven (29%) patients with DMG treated by C7R-GD2.CARTs. Conclusion: Intravenous GD2.CARTs with and without C7R were well tolerated. Patients treated with C7R-GD2.CARTs exhibited transient improvement of neurologic deficits and increased circulating cytokines/chemokines. Treatment with C7R-GD2.CARTs represents a novel approach warranting further investigation for children with these incurable CNS cancers. |
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| معلومات مُعتمدة: | K12 CA090433 United States CA NCI NIH HHS; P30 CA125123 United States CA NCI NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04099797 |
| المشرفين على المادة: | 0 (Receptors, Chimeric Antigen) 65988-71-8 (ganglioside, GD2) 0 (Gangliosides) 0 (IL7R protein, human) 0 (Interleukin-7 Receptor alpha Subunit) |
| تواريخ الأحداث: | Date Created: 20240521 Date Completed: 20240807 Latest Revision: 20240811 |
| رمز التحديث: | 20240812 |
| مُعرف محوري في PubMed: | PMC11305939 |
| DOI: | 10.1200/JCO.23.02019 |
| PMID: | 38771986 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.23.02019 |