Anti-CD28 compositions
Provided herein are novel anti-CD28 x anti-B7H3 (also referred to as “αCD28 x αB7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject αCD28 x αB7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.
1 . A construct comprising a CD28 antigen binding domain (ABD), the CD28 binding domain comprising:
a) a variable heavy domain (VH) the amino acid sequence of SEQ ID NO:880, and b) a variable light domain (VL) having the amino acid sequence of SEQ ID NO:874.
2 . A nucleic acid composition comprising:
a) a first nucleic acid encoding a variable heavy domain (VH) having the amino acid sequence of SEQ ID NO:880; and
b) a second nucleic acid encoding a variable light domain (VL) having the amino acid sequence of SEQ ID NO:874.
3 . An expression vector composition comprising:
a) a first expression vector comprising a first nucleic acid encoding a variable heavy domain (VH) having the amino acid sequence of SEQ ID NO:880; and
b) a second expression vector comprising the second nucleic acid encoding a variable light domain (VL) having the amino acid sequence of SEQ ID NO:874.
4 . A host cell comprising the nucleic acid composition of claim 2 or the expression vector composition of claim 3 .
5 . A method of making a construct comprising culturing the host cell of claim 3 under conditions wherein the construct is expressed and recovering the composition.
6 . An antibody comprising a CD28 binding domain, wherein the CD28 binding domain comprises:
a) a variable heavy domain (VH) having the amino acid sequence of SEQ ID NO:880, and b) a variable light domain (VL) having the amino acid sequence of SEQ ID NO:874.
7 . A nucleic acid composition encoding the antibody of claim 6 .
8 . An expression vector composition comprising the nucleic acid composition of claim 7 .
9 . A host cell comprising the nucleic acid composition of claim 7 or the expression vector composition of claim 8 .
10 . A method of making an antibody comprising culturing the host cell of claim 9 under conditions wherein the antibody is expressed and recovering the antibody.