Immunoactivating antigen-binding molecule
It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.
1. A bispecific antibody comprising:
(1) a single cancer-specific antigen-binding Fab domain;
(2) a single CD137 binding Fab domain; and
(3) an FcRn-binding domain which is a variant antibody Fc region having decreased Fcγ receptor-binding activity compared to the corresponding native Fc region.
2. A pharmaceutical composition comprising as an active ingredient the bispecific antibody of claim 1 .
3. A pharmaceutical composition comprising a combination of a first bispecific antibody of claim 1 , and a second antibody that comprises:
(1) a single cancer-specific antigen-binding Fab domain; and
(2) a single CD3-binding Fab domain.
4. The pharmaceutical composition of claim 3 , wherein the second antibody further comprises an FcRn-binding domain.
5. The pharmaceutical composition of claim 4 , wherein the FcRn-binding domain is a variant antibody Fc region having decreased Fcγ receptor-binding activity compared to the corresponding native Fc region.
6. The bispecific antibody of claim 1 , wherein the single cancer-specific antigen-binding Fab domain binds to Glypican 3.
7. The bispecific antibody of claim 1 , wherein the antibody Fc region having decreased Fcγ receptor-binding activity is a variant IgG2 Fc region.
8. The bispecific antibody of claim 1 , wherein the antibody Fc region having decreased Fcγ receptor-binding activity is a variant IgG4 Fc region.