Therapeutic use of Aldara in chronic myeloid leukemia.
The potent clinical responses seen in patients with chronic myeloid leukemia (CML) after administration of donor-specific lymphocytes, as well as the correlation between the presence of antigen specific T cells and prolonged remission in these patients, suggests a role for the immunological control of CML. Here we propose Aldara, a clinically used formulation of imiquimod, as an agent for augmenting immune responses to CML antigens. Our proposition is based upon 3 tenets: 1) Endogenous dendritic cells (DC) of CML patients, which are known to be derived from the malignant clone, express and present various leukemic antigens; 2) CML-antigen reactive T cell clones exist in the patient but in many situations are ineffectively stimulated to cause significant hematological responses; and 3) Antigen presentation by mature, activated DC, which endogenously express CML-antigens may endow the pre-existing ineffective T cell responses with ability to control CML progression. The practical use of Aldara as a localized activator of DC in the context of present day leukemic therapeutics, as well as various properties of this unique immune modulator will be discussed.
Marleau
Annette M
AM
Medistem Laboratories Inc, Tempe, Arizona, USA. annette.marleau@gmail.com
Lipton
Jeffrey H
JH
Riordan
Neil H
NH
Ichim
Thomas E
TE
D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000077271:Imiquimod; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000077271:Imiquimod