Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule: evidence from phenotyping after rituxan therapy and transfectant cell analyses.

Numerous studies have reported that monoclonal antibody (mAb) FMC7 detects an antigen present on only a subset of circulating B lymphocytes. In particular, this mAb may distinguish typical B-cell chronic lymphocytic leukemia (FMC7 negative) from other types of B-cell non-Hodgkin lymphoma (B-NHL; FMC7 positive). We treated patients with B-NHL with Rituxan, a chimeric CD20 mAb, and observed abrogation of staining not only with prototype CD20 mAb B-1 but also with mAb FMC7. To investigate the relation between antigens CD20 and FMC7, we performed mutual blocking studies that showed mutual inhibition of FMC7 and CD20. In addition, FMC7 modulated CD23 expression and confirmed the presence of mAb B-1 in B-lymphoblastoid cell lines CESS and JVM. Transient transfection of myeloid cell line K562 with plasmid containing CD20-encoding cDNA produced de novo expressions of CD20 and FMC7. Our data indicate that FMC7 binds to a particular conformation of the CD20 antigen, probably to a multimeric CD20 complex. We assume that FMC7 stains positively only when CD20 antigen is present in high densities and in the postulated multimeric complex formation.

Levels of CAF7 (CD98) expression correlate with the complete remission duration in childhood acute leukemia.

The levels of expression of the activation antigen CD98 were studied by mAB CAF7 in 51 newly diagnosed consecutive cases of childhood acute lymphoblastic leukemia aged from 1 to 13 years. The mean follow-up was 8 months. A wide range of CAF7 expression was observed, the highest mean fluorescence intensity exceeding the lowest by 20 times. No correlation was revealed between CAF7 cell surface density on the one hand and sex, age, WBC, platelet count, LDH level, FAB groups and immunophenotypes on the other. A positive association between the levels of CAF7 expression and the complete remission (CR) duration was observed. The group of CAF7(low) patients had a significantly shorter CR duration compared to the CAF7(intermediate) and CAF7(high) cases (P=0.0099). Half of the CAF7(low) patients did not respond to the induction therapy and failed to achieve remission. These correlations were clearly marked in common ALL (cALL), which was usually considered to have a favorable outcome. All CAF7(low) cALL cases had a significantly shorter CR duration (P=0.027). Thus CAF7 appears to provide additional information on the biological characteristics of childhood ALL and may have prognostic value regarding the response to therapy and remission duration.