Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1.
OBJECTIVE
Rituximab, a humanized monoclonal antibody directed to the CD20 antigen present on B lymphocytes, could potentially abrogate the humoral immune response to murine monoclonal antibodies or immunotoxins by depleting antibody-producing B cells.


METHODS
A Phase II study of LMB-1, an immunotoxin targeting the Lewis Y tumor antigen, in combination with rituximab was conducted to test the hypothesis that rituximab could abolish or diminish the development of human antibodies to LMB-1. Five patients were treated in this study and received 375 mg/m(2) rituximab on days 1 and 7 followed by 45 micro g/kg/day LMB-1 on days 10, 12, and 14. The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA.


RESULTS
All five of the patients had a total suppression of circulating CD20/CD19 B-cell population before the administration of the first dose of the immunotoxin. Before rituximab treatment, the mean percentage of CD20/CD19-positive B cells in the five treated patients was 19.8% (range, 4.5-29.8%) of the total peripheral lymphocytes. After two doses of rituximab, CD20/CD19-positive B lymphocytes constituted </=0.1% of the total peripheral lymphocytes. Despite absent circulating antibody-producing B cells, before and during LMB-1 treatment, all of the patients developed neutralizing antibodies to the immunotoxin by day 21 of drug administration, which prevented retreatment.


CONCLUSIONS
Even though rituximab caused complete depletion of circulating CD20/CD19-positive B cells, it had no effect in suppressing the human antibody response to LMB-1 and may be of limited utility in suppressing human antibody responses to other immunogenic proteins.
Hassan
Raffit
R
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA. hassanr@mail.nih.gov
Williams-Gould
Juanita
J
Watson
Thelma
T
Pai-Scherf
Lee
L
Pastan
Ira
I
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000917:Antibody Formation; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000276:immunology; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011549:Pseudomonas / Q000737:chemistry / Q000378:metabolism; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D018941:Antigens, CD19; D018951:Antigens, CD20; D000922:Immunotoxins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D000069283:Rituximab