1. A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia
- Author
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Kathleen Cathcart, David A. Scheinberg, Esperanza B. Papadopoulos, Javier Pinilla-Ibarz, Joseph J. Schwartz, Tatyana Korontsvit, and Victoriya Zakhaleva
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Immunology ,Fusion Proteins, bcr-abl ,Lymphocyte Activation ,Philadelphia chromosome ,Cancer Vaccines ,Biochemistry ,Donor lymphocyte infusion ,Interferon-gamma ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Humans ,Medicine ,Hypersensitivity, Delayed ,business.industry ,ELISPOT ,Myeloid leukemia ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Vaccination ,Leukemia ,Imatinib mesylate ,Vaccines, Subunit ,Female ,Safety ,business ,Chronic myelogenous leukemia - Abstract
A tumor-specific, bcr-abl-derived fusion peptide vaccine can be safely administered to patients with chronic myelogenous leukemia (CML) and can elicit a bcr-abl peptide-specific T-cell immune response. In the present phase 2 trial, 14 patients with CML in chronic phase were vaccinated with 6 fusion peptides mixed with Quillaja saponaria (QS-21). No significant toxic effects were observed. In 14 of 14 patients, delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses developed after beginning vaccinations, and 11 of 14 patients showed interferon-gamma (IFN-gamma) release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. These responses were CD4+CD45RO+. A peptide-specific CD8+ interferon-gamma ELISPOT was found in 4 patients. Four patients in hematologic remission had a decrease in Philadelphia chromosome (Ph) percentage (3 concurrently receiving interferon-alpha and 1 on imatinib mesylate), and 3 patients in molecular relapse after allogenic transplantation became transiently polymerase chain reaction (PCR) negative after vaccination; 2 of these patients received concurrent donor lymphocyte infusion (DLI). All 5 patients on IFN-alpha ultimately reached a complete cytogenetic remission. In conclusion, a tumor-specific bcr-abl breakpoint peptide-derived vaccine can be safely administered and can reliably elicit measurable peptide-specific CD4 immune responses, including in patients after bone marrow transplantation, on interferon, or on imatinib mesylate. A relationship between the clinical responses and vaccination cannot be determined from this trial. (Blood. 2004;103:1037-1042)
- Published
- 2004