Combination of imatinib mesylate with autologous leukocyte-derived heat shock protein and chronic myelogenous leukemia.
OBJECTIVE
To test the feasibility, safety, immunogenicity, and clinical efficacy of an autologous vaccine of leukocyte-derived heat shock protein 70-peptide complexes (Hsp70PC), in conjunction with imatinib mesylate, in patients with chronic myeloid leukemia (CML) in chronic phase.


METHODS
Patients had cytogenetic or molecular evidence of disease, despite treatment with imatinib mesylate for all except one patient, at the beginning of study. Hsp70PCs were purified from the leukopheresed peripheral blood mononuclear cells and were administered in eight weekly intradermal injections at 50 microg/dose without adjuvant. Clinical responses were assessed by bone marrow analysis before and after vaccinations. An IFN-gamma enzyme-linked immunospot assay was used to estimate the effect of treatment on natural killer cells and T cells against CML.


RESULTS
Twenty patients were treated. The manufacturing of Hsp70PCs was successful and the administration was safe for all patients. Minimal or no side effects were reported. Clinical responses were seen in 13 of 20 patients as measured by cytogenetic analysis of bone marrow Philadelphia chromosome-positive cells in metaphases and/or, when possible, the level of Bcr/Abl transcript by PCR. Immunologic responses were observed in 9 of 16 patients analyzed, characterized by an increase in the frequency of CML-specific IFN-gamma-producing cells and IFN-gamma-secreting natural killer cells in the blood. A significant correlation between clinical responses and immunologic responses was observed.


CONCLUSIONS
Autologous Hsp70PC vaccination is feasible and safe. When combined with imatinib mesylate, it is associated with immunologic and possible clinical responses against CML in chronic phase.
Li
Zihai
Z
Center for Immunotherapy of Cancer and Infectious Disease, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA. zli@up.uchc.edu
Qiao
Yi
Y
Liu
Bei
B
Laska
Elizabeth J
EJ
Chakravarthi
Priyamvadha
P
Kulko
Judith M
JM
Bona
Robert D
RD
Fang
Min
M
Hegde
Upendra
U
Moyo
Victor
V
Tannenbaum
Susan H
SH
Ménoret
Antoine
A
Gaffney
Judy
J
Glynn
Laura
L
Runowicz
Carolyn D
CD
Srivastava
Pramod K
PK
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005240:Feasibility Studies; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000096:biosynthesis; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D001549:Benzamides; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D010879:Piperazines; D011743:Pyrimidines; D007371:Interferon-gamma; D000068877:Imatinib Mesylate