IMCT-10A PHASE I DOSE ESCALATION STUDY TO TEST THE SAFETY OF INTRATUMORAL ADOPTIVE IMMUNE THERAPY WITH AlloCTL IN RECURRENT GLIOMA PATIENTS
| Autor: | Janet Treger, Colin C. Malone, Robert M. Prins, Linda M. Liau, Edward Ha, Emma Young, Michelle J. Hickey, Horacio Soto, Carol A. Kruse, Kate L. Erickson |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty business.industry medicine.medical_treatment Immunotherapy Recurrent Glioma Mixed lymphocyte reaction medicine.disease Peripheral blood mononuclear cell Tumor progression Glioma Internal medicine Immunology Toxicity Medicine Cytotoxic T cell Neurology (clinical) business Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology |
| Popis: | In a Phase 1 dose escalation study we evaluated the safety, feasibility, toxicity, and survival of patients treated with allogeneic cytotoxic T lymphocytes and recombinant IL-2 (alloCTL, rIL-2) infusion administered to the resection cavity of patients with recurrent glioma (WHO grade III or IV). AlloCTL are generated when gamma-irradiated lymphoblasts from the brain tumor patient stimulate the proliferation of peripheral blood mononuclear cells (PBMC) isolated from an HLA-disparate healthy donor in ex vivo culture via one-way mixed lymphocyte reaction. Nine patients were treated on the protocol and received a range of 0.5-5 cycles of therapy. Patients and donors were mismatched at a minimum of 2 HLA A, B, DR loci. Infusates were at least 30% CD3+. Cytotoxicity of alloCTL against patient PBMC ranged from 21.0-84.4% at a 30:1 effector to target ratio. The ratio of CD4/CD8 T cells averaged 1.12 (range 0.14-2.95). In vitro restimulation of alloCTL with patient lymphoblasts allowed for quantitation of immune cell subset proliferation and production of IFN-γ. Adverse events were noted at all three dose levels tested, and were primarily limited to Grade 1-2. Grade 3-4 events were noted only at dose levels 2 and 3. One patient experienced a dose limiting toxicity characterized by Grade 3 fatigue, arthralgia, headache, and non-infectious meningitis. Patient serum samples were collected during the course of therapy to determine Th1/Th2 cytokine profiles using Luminex multiplex analysis. Tumor progression was evident in 8/9 patients resulting in removal from the clinical trial. Median overall survival from the time of inclusion into the study was 8.8 months (range- 3.6-35.7 months). Two patients are still alive at greater than 35.7 and 16.4 months. The results suggest that alloCTL infusion is safe, feasible, and may warrant further study based on the clinical results. |
| Databáze: | OpenAIRE |
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