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High dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM)

¹ Department of Internal Medicine III, University of Ulm, Germany
² Department of Internal Medicine III, University of Rostock, Germany
³ Institute of Clinical Transfusion Medicine, University of Ulm, Germany
⁴ Ludwig Institute of Cancer Research, New York Branch, USA

Correspondence: Jochen Greiner, Department of Internal Medicine III, University of Ulm, Albert-Einstein-Allee 23 89081 Ulm, Germany. E-mail: jochen.greiner{at}uniklinik-ulm.de

ABSTRACT

Background: Recently, we demonstrated immunological and clinical responses to a RHAMM-R3 peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndrome (MDS) and multiple myeloma (MM). To improve the outcome of the vaccine, a second cohort was vaccinated with a higher dose of 1,000µg peptide.

Design and Methods: Nine patients received four vaccinations subcutaneously at a biweekly interval. Immunomonitoring of cytotoxic CD8+ as well as regulatory CD4+ T cells was performed by flow cytometry as well as by enzyme-linked immunospot (ELISpot) assays. Parameters of clinical response were assessed.

Results: In four of nine patients (44%) we detected positive immunological responses. These patients showed an increase of CD8+RHAMM-R3_tetramer+/CD45RA+/CCR7–/CD27–/CD28– effector T cells and an increase of R3-specific CD8+ T cells. Two of these patients showed a significant decrease of regulatory T cells (Tregs). In one patient without response Tregs frequency increased from 5 to 16%. Three patients showed clinical effects: One patient with MDS RAEB-1 showed a reduction of leukemic blasts in the bone marrow, another MDS patient an improvement of peripheral blood counts and one patient with MM a reduction of free light chains. In comparison with the 300 µg cohort clinical and immunological reactions were lower in this cohort.

Conclusions: High dose RHAMM-R3 peptide vaccination induced immunological responses and positive clinical effects. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematological malignancies. However, higher doses of peptide did not improve the frequency and intensity of immune responses in this trial.

Key words: acute myeloid leukemia (AML), leukemia-associated antigens (LAAs), receptor for hyaluronic acid mediated motility (RHAMM/CD168), epitope peptides, cancer vaccines.