Antibodies and methods of use thereof

A method of modulating an immune response in a subject in need thereof, the method comprising administering to the subject an effective amount of a multispecific antibody comprising a first antigen-binding region that specifically binds human OX40 and a second antigen-binding region that specifically binds human GITR, wherein:

• a. the first antigen-binding region comprises a first heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3, and a first light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein the first heavy chain comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of the VH amino acid sequence of SEQ ID NO:
• 54, and the first light chain comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of the VL amino acid sequence of SEQ ID NO:
• 55 and
• b. the second antigen-binding region comprises a second antibody heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3 and a second antibody light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein:
• i. the VH-CDR1 comprises the amino acid sequence of X1YX2MX3 (SEQ ID NO:87), wherein X1 is D, E or G;
• X2 is A or V;
• and X3 is Y or H;
• ii. the VH-CDR2 comprises the amino acid sequence of X1IX2TX3SGX4X5X6YNQKFX7X8(SEQ ID NO:88), wherein X1 is V or L;
• X2 is R, K or Q;
• X3 is Y or F;
• X4 is D, E or G;
• X5 is V or L;
• X6 is T or S;
• X7 is K, R or Q;
• and X8 is D, E or G;
• iii. the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:3;
• iv. the VL-CDR1 comprises the amino acid sequence of KSSQSLLNSX1NQKNYLX2 (SEQ ID NO:90), wherein X1 is G or S;
• and X2 is T or S;
• v. the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:5;
• and
• vi. the VL-CDR3 comprises the amino acid sequence of QNX1YSX2PYT (SEQ ID NO:92), wherein X1 is D or E;
• and X2 is Y, F or S.