Aims: 

Despite aggressive chemotherapy the majority of T-cell malignancies have an unfavourable prognosis. Therefore, more potent targeted therapies with greater specificity and more favourable toxicity profiles are needed. One of the prerequisites for successful immunotherapy is the selection of an appropriate target antigen, which ideally should be T-cell specific and expressed on most T-cell lymphomas and leukaemias but absent on at least a portion of normal T lymphocytes. The T-cell differentiation antigen CD7 meets these requirements. A high affinity CD7 hybridoma antibody – generated by our group – produced significant anti-tumour effects in xenotransplanted athymic nude and SCID mice. The Fc portion was essential for the anti-tumour effect in vivo. Here the construction and expression of a chimeric CD7 mini-antibody – to enhance recruitment of human effector cells – is described.

Methods: 

The CD7 mini-antibody was expressed in 293T cells and purified to homogeneity by two-step purification. To monitor binding to antigen positive and negative cells, FACS analyses were performed. Lytic activity was tested in 51Cr-release assays.

Results: 

The recombinant protein was successfully expressed and specifically bound to CD7-positive CEM cells. In ADCC experiments the mini-antibody mediated efficient lysis of CEM cells with MNC as effector cells. No killing was observed with CD7-negative ARH-77 cells.

Conclusions: 

The CD7 mini-antibody retained its antigen specificity and significantly mediated ADCC – an important mechanism of action of therapeutic antibodies – with human MNC as effector cells. This novel reagent might have potential for the treatment of T-cell malignancies.

This work was supported by intramural funding of the University of Kiel