Binding molecules to CD38 and PD-L1
The present invention relates to a bispecific molecule comprising at least one anti-CD38 domain and at leak one anti-PD-L1 domain, which are capable of simultaneous binding to CD38 and PD-L1 antigens, respectively.
1. A bispecific molecule comprising at least one anti-CD38 domain and at least one anti-PD-L1 domain, which are capable of simultaneous binding to CD38 and PD-L1 antigens, respectively, wherein the bispecific molecule is a full length antibody comprising two heavy chains and four light chains,
wherein each heavy chain comprises
a) a Fc region comprising Hinge-CH2-CH3 domains,
b) which Fc region is linked to Fab heavy chain (CH1-VH) of atezolizumab,
c) which in turn is linked to Fab heavy chain (CH1-VH) of daratumumab, by a hinge-derived polypeptide linker sequence, wherein said polypeptide linker sequence links the N-terminus of Fab heavy chain VH domain of atezolizumab with the C-terminus of CH1 domain of daratumumab,
wherein the Fc region comprises a Hinge domain of SEQ ID NO: 26, a CH2 domain of SEQ ID NO: 27 and a CH3 domain of SEQ ID NO: 28; wherein the Fab heavy chain of atezolizumab comprises a VH domain of SEQ ID NO: 24 and a CH1 domain of SEQ ID NO: 25; and wherein the Fab heavy chain of daratumumab comprises a VH domain of SEQ ID NO: 22 and a CH1 domain of SEQ ID NO: 23;
and wherein two light chains comprise SEQ ID NO: 11 and two other light chains comprise SEQ ID NO: 12.
2. The bispecific molecule of claim 1 , said bispecific molecule comprising a) two heavy chains, each comprising SEQ ID NO: 10 and b) four light chains, two comprising SEQ ID NO: 11 and the other two comprising SEQ ID NO: 12.
3. A method for producing a bispecific molecule, said method comprising the following steps:
a) culturing in suitable medium and culture conditions a host cell expressing an antibody heavy chain and antibody light chains according to claim 1 , and
b) recovering said bispecific molecules from the culture medium or from said cultured cells.
4. A method of treating cancer comprising administering a bispecific molecule according to claim 1 to a subject having cancer.
5. The method according to claim 4 , wherein said cancer is multiple myeloma, lymphoma or leukemia.
6. The bispecific molecule of claim 1 , wherein the polypeptide linker sequence comprises the amino acid sequence:
EPKX1CDKX2HX3X4PPX5PAPELLGGPX6X7PPX8PX9PX10GG (SEQ ID NO: 13),
wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, and X10, identical or different, are any amino acid.
7. The bispecific molecule of claim 1 , wherein the polypeptide linker sequence comprises SEQ ID NO: 15.