Antibodies to MICA and MICB proteins
MICA and MICB are expressed on the surface of stressed, virus infected and cancer cells; they bind to their common receptor NKG2D on immune effector cells such as natural killer (NK) cells and some T cells to signal immune responses, including cytotoxicity, towards cells expressing surface MICA or MICB. To evade this immune-surveillance, virus infected cells and cancer cells shed the extracellular domain of their MICA and MICB as soluble forms (sMICA and sMICB) which act as decoys by binding and down-regulating expression of NKG2D on the immune effector cells. Antibodies are provided that specifically bind the soluble forms of both MICA and MICB to inhibit their adverse effects, but do not bind cell- or membrane-bound MICA and MICB to preserve their beneficial immune effects.
1. An isolated antibody having a CDR L1 consisting of the amino acid sequence RSSKSLLQSNGNTFLY (SEQ ID NO:86); a CDR L2 consisting of the amino acid sequence RMSNLAS (SEQ ID NO:87); a CDR L3 consisting of the amino acid sequence MQHLEYPFT (SEQ ID NO:88); a CDR H1 consisting of an amino acid sequence NYGMN (SEQ ID NO:92), a CDR H2 consisting of the amino acid sequence WINTNTGEPTYAEEFKG (SEQ ID NO:93); and a CDR H3 consisting of the amino acid sequence SGGSSPFAY (SEQ ID NO:94), wherein the antibody specifically binds soluble MICA or soluble MICB.
2. The isolated antibody of claim 1 , comprising a light chain variable region (VL) consisting of the amino acid sequence of SEQ ID NO: 31 and a heavy chain variable region (VH) consisting of the amino acid sequence of SEQ ID NO: 35.
3. A pharmaceutical composition comprising an isolated antibody of claim 1 or 2 , and a pharmaceutically acceptable carrier.