Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study.
Peptides from the e14a2 BCR-ABL junction will elicit T-cell responses in vitro. Here, 19 imatinib treated CML patients in first chronic phase were vaccinated with BCR-ABL peptides spanning the e14a2 fusion junction, some of which were linked to the pan DR epitope PADRE to augment CD4+ T cell help. Six vaccinations were given over 9 weeks, together with sargramostim. All patients developed mild local reactions. T cell responses to PADRE were seen in all patients. Fourteen of 19 patients developed T cell responses to BCR-ABL peptides. The development of an anti-BCR-ABL T cell response correlated with a subsequent fall in BCR-ABL transcripts. No molecular benefit was seen in the 5 patients not in major cytogenetic response (MCR) at baseline. However, of the 14 patients in MCR at baseline, 13 developed at least 1 log fall in BCR-ABL transcripts, though this occurred several months after completing vaccination, consistent with an effect at a primitive CML stem cell level. Vaccination may improve the fall in BCR-ABL transcripts in patients who have received imatinib for more than 12 months. BCR-ABL peptide vaccination may improve control of CML, especially in patients responding well to imatinib. Randomised trials are required to address this further.
Rojas
J M
JM
Department of Haematology, University of Liverpool, Liverpool, UK.
Knight
K
K
Wang
L
L
Clark
R E
RE
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D015496:CD4-Positive T-Lymphocytes; D019496:Cancer Vaccines / Q000737:chemistry* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D019496:Cancer Vaccines; D010455:Peptides; D010879:Piperazines; D011743:Pyrimidines; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl