Safety of WT1 and PR1 Peptide Vaccination for Patients With Myeloid Malignancies
Myeloid malignancies including acute myeloid leukemia and the related disorders
myelodysplastic syndrome (MDS) and myeloproliferative diseases represent a wide group of
bone marrow stem cell malignancies. Some patients can be cured with chemotherapy or by
allogeneic stem cell transplantation. However, a proportion of patients progress following
chemotherapy and some relapse after transplantation. Therefore, there is need for studies of
investigational agents to improve management of these patients.
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell
transplantation suggests that stimulating the patient's own T cell responses to MDS and
leukemia with a vaccine might also retard disease progression and even achieve disease
remissions. WT1 and PR1 were identified as target antigens because both antigens are highly
expressed by CD34+ stem cells of most patients with myeloid malignancies but not by normal
marrow cells. An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could
induce T cell response against MDS and leukemic cells while sparing normal cells and by
using a combination of two antigens the risk of disease escape by antigen down regulation
should be further diminished.
Therefore, we propose to evaluate a vaccine composed of peptides derived from two proteins
over-expressed in MDS and leukemia stem cells - proteinase 3 (PR1) and Wilms tumor-1 (WT1).
This protocol, the first in a series of planned research, will evaluate the safety of a
single dose of a combination of two peptide vaccines, namely PR1:169-177 and WT-1:126-134 in
Montanide adjuvant administered concomitantly with GM-CSF (Sargramostim) in select subjects
diagnosed with MDS, AML and CML.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie...
Gregory J Kato, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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