Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies.
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), beta-2-microglobulin (beta-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 beta-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.
Albitar
Maher
M
Department of Hematopathology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92690-6130, USA. maher.x.albitar@questdiagnostics.com
Do
Kim-Anh
KA
Johnson
Marcella M
MM
Giles
Francis J
FJ
Jilani
Iman
I
O'Brien
Susan
S
Cortes
Jorge
J
Thomas
Deborah
D
Rassenti
Laura Z
LZ
Kipps
Thomas J
TJ
Kantarjian
Hagop M
HM
Keating
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D000074301:CD52 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011233:Precipitin Tests; D011379:Prognosis; D001613:beta 2-Microglobulin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007135:Immunoglobulin Variable Region; D001613:beta 2-Microglobulin; D000074323:Alemtuzumab