Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies

Maher Albitar, Kim Anh Do, Marcella M. Johnson, Francis J. Giles, Iman Jilani, Susan O'Brien, Jorge Cortes, Deborah Thomas, Laura Z. Rassenti, Thomas J. Kipps, Hagop M. Kantarjian, Michael Keating

Research output: Contribution to journalArticle

Abstract

BACKGROUND. The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS. The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS. The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), β-2-microglobulin (β-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for β-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS. These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.

Original languageEnglish (US)
Pages (from-to)999-1008
Number of pages10
JournalCancer
Volume101
Issue number5
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Tumor Biomarkers
Anti-Idiotypic Antibodies
Therapeutics
Antigen-Antibody Complex
Immunosorbents
alemtuzumab
Physiologic Monitoring
Immunoprecipitation
Eosinophils
Monocytes
Glycoproteins
B-Lymphocytes
Western Blotting
Cell Membrane
T-Lymphocytes
Enzymes

Keywords

  • Alemtuzumab
  • CAMPATH-1H
  • Chronic lymphocytic leukemia
  • Plasma
  • Soluble CD52
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Albitar, M., Do, K. A., Johnson, M. M., Giles, F. J., Jilani, I., O'Brien, S., ... Keating, M. (2004). Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer, 101(5), 999-1008. https://doi.org/10.1002/cncr.20477

Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. / Albitar, Maher; Do, Kim Anh; Johnson, Marcella M.; Giles, Francis J.; Jilani, Iman; O'Brien, Susan; Cortes, Jorge; Thomas, Deborah; Rassenti, Laura Z.; Kipps, Thomas J.; Kantarjian, Hagop M.; Keating, Michael.

In: Cancer, Vol. 101, No. 5, 01.09.2004, p. 999-1008.

Research output: Contribution to journalArticle

Albitar, M, Do, KA, Johnson, MM, Giles, FJ, Jilani, I, O'Brien, S, Cortes, J, Thomas, D, Rassenti, LZ, Kipps, TJ, Kantarjian, HM & Keating, M 2004, 'Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies', Cancer, vol. 101, no. 5, pp. 999-1008. https://doi.org/10.1002/cncr.20477
Albitar, Maher ; Do, Kim Anh ; Johnson, Marcella M. ; Giles, Francis J. ; Jilani, Iman ; O'Brien, Susan ; Cortes, Jorge ; Thomas, Deborah ; Rassenti, Laura Z. ; Kipps, Thomas J. ; Kantarjian, Hagop M. ; Keating, Michael. / Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. In: Cancer. 2004 ; Vol. 101, No. 5. pp. 999-1008.
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abstract = "BACKGROUND. The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS. The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS. The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), β-2-microglobulin (β-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for β-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS. These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.",
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T1 - Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies

AU - Albitar, Maher

AU - Do, Kim Anh

AU - Johnson, Marcella M.

AU - Giles, Francis J.

AU - Jilani, Iman

AU - O'Brien, Susan

AU - Cortes, Jorge

AU - Thomas, Deborah

AU - Rassenti, Laura Z.

AU - Kipps, Thomas J.

AU - Kantarjian, Hagop M.

AU - Keating, Michael

PY - 2004/9/1

Y1 - 2004/9/1

N2 - BACKGROUND. The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS. The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS. The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), β-2-microglobulin (β-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for β-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS. These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.

AB - BACKGROUND. The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS. The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS. The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), β-2-microglobulin (β-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for β-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS. These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.

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KW - CAMPATH-1H

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KW - Plasma

KW - Soluble CD52

KW - Survival

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