CPC C07K 16/2809 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 16/2803 (2013.01); C07K 16/283 (2013.01); C07K 16/2878 (2013.01); C12N 5/0634 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01)] | 26 Claims |
1. A method of treating a solid cancer in a human subject in need thereof, wherein the solid cancer is a solid cancer selected from the group consisting of colon cancer, breast cancer, renal cancer, melanoma, prostate cancer, lung cancer, rectal cancer, colorectal cancer and cervical cancer, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a multispecific molecule,
wherein the multispecific molecule comprises a first domain that binds to a first target molecule expressed by a subset of T cells of the human subject and a second domain that binds to a second target molecule expressed by T cells of the human subject;
wherein the first target molecule is a human T cell receptor beta chain (TCR(3) subfamily member;
wherein the multispecific molecule is a TCR agonist;
wherein the second domain comprises a cytokine, wherein
(i) the cytokine is a human IL-2 having a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280,
(ii) the cytokine is a human IL-12 having a sequence with at least 90% sequence identity to SEQ ID NO: 2290;
(iii) the cytokine is a human IL-15 having a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 2170 and 2320, or
(iv) the cytokine is a human IL-21 having a sequence with at least 90% sequence identity to SEQ ID NO: 2193;
wherein the multispecific molecule binds to a human T cell receptor beta variable region (TCRβV) of the human TCRβ expressed by the subset of T cells of the human subject; and
wherein binding of the first domain to the TCRβV and binding of the second domain to the second target molecule promote the subset of T cells to kill cancer cells.
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