Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses

Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor-specific an tigen that is also the oncogenic protein required for neoplasia. CML is cha racterized by the t(9;22) that results in the bcr-abl fusion oncogene and i n the expression of a chimeric protein product p210, Previously we have sho wn that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and c lass II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine, We evaluate d the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each rec eived either 50 mu g, 150 mu g, 500 mu g, or 1500 mu g total peptide mixed with 100 mu g QS-21 as an immunological adjuvant, Delayed-type hypersensiti vity (DTH), humoral responses, and unprimed ex vivo autologous proliferatio n (H-3-thymidine incorporation) and cytotoxicity (chromium-51 release) resp onses were measured. All 68 vaccinations were well tolerated without signif icant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3 ) and/or DTH responses (n = 2) were generated that lasted up to 5 months af ter vaccination. Cytotoxic T lymphocytes have not been identified. In concl usion, a tumor-specific, bcr-abl derived peptide vaccine can be safely admi nistered to patients with chronic-phase CML and can elicit a bcr-abl peptid e-specific immune response despite the presence of active disease in these patients and approximately 10(12) leukemia cells. (C) 2000 by The American Society of Hematology.