Heat shock protein 70-based vaccine stimulates both innate and adaptive immunity against chronic myeloid leukemia

Abstract

2515 Background: HSP70 chaperones both proteins and antigenic peptides. Vaccination with tumor-derived HSP70-peptide complexes elicits anti-tumor immunity in murine models. We have earlier reported that HSP70 vaccines can be effectively produced from peripheral blood mononuclear cells (PBMCs) of patients with chronic myeloid leukemia (CML) in chronic phase. Moreover, eight weekly injections of 50 μg autologous HSP70 vaccines were associated with no grade II or higher toxicity in any patients and with clinical efficacies in 11 out of 17 patients. In the present study, the immunological responses to this vaccine were studied. Methods: All patients in the study had either cytogenetic or molecular evidence of diseases, despite Imatinib Mesylate, prior to the study entry. Peripheral blood was obtained, before the 1st and 5th vaccines, and two weeks after the 8th vaccine. IFNγ-producing effector cells in PBMCs were measured by an ELISPOT assay using a variety of targets, including HLA negative but Bcr/Abl+ K562 cell lines, HSP70-peptide complexes or K562 lysates. A pan-HLA class I specific antibody W6/32 was used to determine if IFNγ production was MHC restricted or not. Results: The frequency of IFNγ-producing cells in the PBMCs, in response to HSP70-peptide complexes, was increased in nine out of 12 patients analyzed. This activity was significantly blocked by W6/32, indicating that peptides bound to HSP70 can be cross-presented to HLA class I to activate CD8+ T cells. The incomplete blockage by W6/32 indicates that HSP70 can stimulate IFNγ production by other cells, in a peptide-independent manner. Indeed, natural killer (NK) cell activity post vaccinations, as measured against the standard NK target K562, increased markedly in 12 out of 15 patients. We have also confirmed an increased frequency of CML-specific and HLA class I-restricted T cells using K562 cell lysates as targets. Conclusion: The autologous HSP70-based vaccine induces both NK and CML-specific T cell immunity in a majority of patients. The remarkable immunologic activity of HSP70 suggests that it has adjuvant therapeutic values for CML. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigenics Antigenics Antigenics