Composition for treating malignant myeloma or other CD138-positive tumors, comprises a ULBP2-antiCD138 protein for stimulating an immune response through the NKG2D receptor

摘要

Composition (A) for treating malignant myeloma, by activating an antitumor immune response through stimulation of the NKG2D receptor, comprises the protein ULBP2 (UL16-binding protein 2)/anti-CD138 (I), in a carrier material. An independent claim is also included for use of ULBP2-encoding DNA or RNA for preparing a construct analogous to (I) but with the CD138-binding component replaced by an antibody fragment directed against another selected tumor antigen (Ag) for treating malignant disease in which Ag is expressed. ACTIVITY : Cytostatic. Natural killer (NK) cells from healthy donors were used as effector cells (EC) in a europium-release assay. Target cells (TC) were human multiple myeloma cells U266 and were labeled with Eu; then incubated with NK and the amount of EU released into the supernatant determined as a measure of NK-induced tumor cell lysis. In presence of 5 mu g/ml of the fusion protein between ULBP2 and anti-CD138 single-chain antibody fragment, lysis was 50% at EC:TC ratio 10:1; compare 30% for 15 mu g/ml of the antibody fragment alone. A similar result was found for RPMI-8226 cells, also positive for CD138, but not for 293T cells, negative for CD138. MECHANISM OF ACTION : Activation of an anti-tumor immune response by stimulation of the NKG2D receptor (present on natural killer cells, for which ULBP2 is a ligand), resulting in lysis of target cells.