Combination of Imatinib Mesylate with Autologous Leukocyte-Derived Heat Shock Protein and Chronic Myelogenous Leukemia

Purpose: 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. Experimental Desig...

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Published in:	Clinical cancer research Vol. 11; no. 12; pp. 4460 - 4468
Main Authors:	Li, Zihai, Qiao, Yi, Liu, Bei, Laska, Elizabeth J, Chakravarthi, Priyamvadha, Kulko, Judith M, Bona, Robert D, Fang, Min, Hegde, Upendra, Moyo, Victor, Tannenbaum, Susan H, Ménoret, Antoine, Gaffney, Judy, Glynn, Laura, Runowicz, Carolyn D, Srivastava, Pramod K
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-06-2005
Subjects:	Adult Aged Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Benzamides Biological and medical sciences Cancer Vaccines - administration & dosage Cancer Vaccines - immunology chronic myeloid leukemia Cytotoxicity, Immunologic - drug effects Dendritic cell Feasibility Studies Female heat shock protein 70 Heat-Shock Proteins - administration & dosage Heat-Shock Proteins - immunology Hematologic and hematopoietic diseases Humans Imatinib Mesylate Interferon-gamma - biosynthesis K562 Cells Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Leukocytes - metabolism Male Medical sciences Middle Aged NK cell Pharmacology. Drug treatments Piperazines - administration & dosage Pyrimidines - administration & dosage T-Lymphocytes - drug effects T-Lymphocytes - immunology Treatment Outcome Tumor vaccine Myeloproliferative syndrome Chronic Leukocyte Chronic myelocytic leukemia Heat shock protein Malignant hemopathy Autologous system
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Summary:	Purpose: 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. Experimental Design: 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 μg/dose without adjuvant. Clinical responses were assessed by bone marrow analysis before and after vaccinations. An IFN-γ 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-γ-producing cells and IFN-γ-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.
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ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-05-0250