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

Authors' Affiliations: ¹ Center for Immunotherapy of Cancer and Infectious Disease, ² General Clinical Research Center, and ³ University of Connecticut Cancer Center, University of Connecticut School of Medicine, Farmington, Connecticut

Requests for reprints: Zihai Li, Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1601. Phone: 860-679-7979; Fax: 860-679-1265; E-mail: zli{at}up.uchc.edu.

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- 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--producing cells and IFN--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.

Key Words: Tumor vaccine • chronic myeloid leukemia • heat shock protein 70 • NK cell • Dendritic cell

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