Details

Autor(en) / Beteiligte

• Greiner, Jochen
• Schmitt, Anita
• Giannopoulos, Krzysztof
• Rojewski, Markus T
• Götz, Marlies
• Funk, Isabel
• Ringhoffer, Mark
• Bunjes, Donald
• Hofmann, Susanne
• Ritter, Gerd
• Döhner, Hartmut
• Schmitt, Michael

Titel

High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma

Ist Teil von

• Haematologica (Roma), 2010-07, Vol.95 (7), p.1191-1197

Ort / Verlag

Pavia: Ferrata Storti Foundation

Erscheinungsjahr

2010

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Recently, we demonstrated immunological and clinical responses to a RHAMM-R3 peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. To improve the outcome of the vaccine, a second cohort was vaccinated with a higher dose of 1,000 microg peptide. 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. In 4 of 9 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 myelodysplastic syndrome RAEB-1 showed a reduction of leukemic blasts in the bone marrow, another myelodysplastic syndrome patient an improvement of peripheral blood counts and one patient with multiple myeloma a reduction of free light chains. Clinical and immunological reactions were lower in this cohort than in the 300 microg cohort. 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 hematologic malignancies. However, higher doses of peptide did not improve the frequency and intensity of immune responses in this trial.