A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint.

Autor: Bever KM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Thomas DL 2nd; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Zhang J; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Diaz Rivera EA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Rosner GL; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Zhu Q; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Nauroth JM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Christmas B; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Thompson ED; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Anders RA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Judkins C; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Liu M; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Jaffee EM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA., Ahuja N; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Departments of Surgery, Oncology, and Pathology, Smilow Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA., Zheng L; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Azad NS; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, Baltimore, MD, 21287, USA. nazad2@jhmi.edu.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2021 Feb 02; Vol. 13 (1), pp. 25. Date of Electronic Publication: 2021 Feb 02.
DOI: 10.1186/s13148-021-01014-8
Abstrakt: Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoint of change in CD45RO + T cells. 18 patients with advanced CRC enrolled, 11 underwent paired biopsies and were evaluable for the primary endpoint. No significant increase in CD45RO + cells was noted. Grade 3-4 toxicities were expected and manageable. Guadecitabine + GVAX was tolerable but demonstrated no significant immunologic activity in CRC. We report a novel trial design to efficiently evaluate investigational therapies with a primary pharmacodynamic endpoint.Trial registry Clinicaltrials.gov: NCT01966289. Registered 21 October, 2013.
Databáze: MEDLINE
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