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PR1 Peptide Antigen

Last updated on November 21, 2020

PR1 Peptide AntigenThe M.D. Anderson Cancer Center is investigating the human leukemia-associated antigen, PR1, as a potential treatment for acute myeloid leukemia (acute myelogenous leukemia) and chronic myelogenous leukemia. The agent is in Phase II clinical trials.

PR1 is derived from proteinase 3, an aberrantly expressed protein in myeloid leukemia cells, and can be presented on HLA-A2 to CTLs that preferentially kill leukemic cells over normal hematopoietic progenitors.

Results were presented at the 46th ASH meeting in 2004 from a trial in which 35 HLA-A2+ patients with acute myelogenous leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia were vaccinated with the PR1 peptide in an incomplete Freund’s adjuvant (an agent used in vaccine therapy to stimulate the immune system) and 75 mg of granulocyte-macrophage colony-stimulating factor (GM-CSF). The chronic myelogenous leukemia patients either had not responded to first-line treatment or had relapsed disease. Patients were assigned at random to receive 0.25 mg, 0.50

mg, or 1.0 mg PR1 subcutaneously every three weeks for three total injections. Immune responses were assessed by PR1/HLA-A2 tetramer staining and intra-cellular interferon-gamma (IFN-y) production by CTLs. Clinical responses were assessed by bone marrow biopsy both before study entry and three weeks after the third vaccination. The patients had a median age of 50 and were treated for a median of 26 months from time of diagnosis. Follow-up lasted one to four years.

Immune responses were elicited in 60% of the evaluable patients versus 0% among patients without an immune response. Progression-free survival for patients with and without immune response was 6.4 months versus 2.4 months, respectively. Of ten chronic myelogenous leukemia patients, one achieved a cytogenetic response. Three chronic myelogenous leukemia patients refractory to allo-Stem-cell transplantation, interferon-a, and imatinib experienced stable disease with some hematologic improvement and were able to discontinue hydroxyurea.

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