Therapeutic use of Aldara in chronic myeloid leukemia.

Author

Marleau AM, Lipton JH, Riordan NH, Ichim TE.

Journal

J Transl Med. 2007 Jan 25;5:4

Abstract

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.

Content

1/1/2007

J Transl Med. 2007 Jan 25;5:4

Marleau AM, Lipton JH, Riordan NH, Ichim TE.

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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1790884/

Adaptive Immunity / Drug Effects; Adaptive Immunity / Immunology; Adjuvants; Immunologic / Pharmacology; Adjuvants; Immunologic / Therapeutic Use; Aminoquinolines / Pharmacology; Aminoquinolines / Therapeutic Use*; Humans; Imiquimod; Immunity; Innate / Drug Effects; Immunity; Innate / Immunology; Leukemia; Myelogenous; Chronic; Bcr-Abl Positive / Drug Therapy*; Leukemia; Myelogenous; Chronic; Bcr-Abl Positive / Immunology