Safety and immunologic correlates of Melanoma GVAX, a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting
| Autor: | Brandon Luber, Theresa S. Pritchard, Shuming Chen, Irwin Freed, Tracee L. McMiller, Janice Davis Sproul, Susan Sartorius-Mergenthaler, Hao Wang, Sowmya Ravi, Drew M. Pardoll, Evan J. Lipson, Suzanne L. Topalian, William H. Sharfman, Janis M. Taube, January T. Salas |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Biopsy medicine.medical_treatment Dose-Response Relationship Immunologic Cell Count Cancer Vaccines T-Lymphocytes Regulatory Monocytes General Biochemistry Genetics and Molecular Biology Melanoma Vaccine Young Adult Immune system medicine Humans Melanoma Cyclophosphamide Adjuvant Aged Medicine(all) Biochemistry Genetics and Molecular Biology(all) business.industry Research Monocyte Immunity Granulocyte-Macrophage Colony-Stimulating Factor GM-CSF General Medicine Dendritic cell Middle Aged medicine.disease GVAX 3. Good health Radiography Vaccination medicine.anatomical_structure Immunology Disease Progression Female Immunotherapy Peptides business Vaccine |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | Background Limited adjuvant treatment options exist for patients with high-risk surgically resected melanoma. This first-in-human study investigated the safety, tolerability and immunologic correlates of Melanoma GVAX, a lethally irradiated granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting allogeneic whole-cell melanoma vaccine, administered in the adjuvant setting. Methods Patients with stage IIB-IV melanoma were enrolled following complete surgical resection. Melanoma GVAX was administered intradermally once every 28 days for four cycles, at 5E7 cells/cycle (n = 3), 2E8 cells/cycle (n = 9), or 2E8 cells/cycle preceded by cyclophosphamide 200 mg/m2 to deplete T regulatory cells (Tregs; n = 8). Blood was collected before each vaccination and at 4 and 6 months after treatment initiation for immunologic studies. Vaccine injection site biopsies and additional blood samples were obtained 2 days after the 1st and 4th vaccines. Results Among 20 treated patients, 18 completed 4 vaccinations. Minimal treatment-related toxicity was observed. One patient developed vitiligo and patches of white hair during the treatment and follow-up period. Vaccine site biopsies demonstrated complex inflammatory infiltrates, including significant increases in eosinophils and PD-1+ lymphocytes from cycle 1 to cycle 4 (P |
| Databáze: | OpenAIRE |
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