Pharmaceutical composition for treatment of cancer, comprising an immune checkpoint inhibitor antibody and a fusion protein comprising an IL-2 mutant and a CD80 extracellular domain
There is provided a pharmaceutical composition for preventing or treating cancer comprising, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor. The fusion protein containing an CD80 fragment, an Fc domain of an immunoglobulin, and an IL-2 variant in an embodiment can activate immune cells such as natural killer cells as well as control the immune cell regulatory activity of regulatory T cells. In addition, the combined administration of the fusion protein and an immune checkpoint inhibitor such as Keytruda known as a PD-1 inhibitor can effectively inhibit cancer. Therefore, a pharmaceutical composition containing, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor can be effectively applied to the treatment of cancer and has high industrial applicability.
1. A pharmaceutical composition comprising, as active ingredients, a fusion protein dimer comprising an IL-2 protein variant comprising substitutions of the 38th and 42nd in the amino acid of SEQ ID NO: 10 and an extracellular domain of CD80 protein; and an immune checkpoint inhibitor selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody and an anti-TIGIT antibody.
2. The pharmaceutical composition according to claim 1 , wherein the IL-2 protein variant and the extracellular domain of CD80 protein are linked to each other via a linker.
3. The pharmaceutical composition according to claim 1 , wherein the extracellular domain of CD80 consists of the 35 th to 242 nd amino acid sequence of SEQ ID NO: 11.
4. The pharmaceutical composition according to claim 1 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 9.
5. The pharmaceutical composition according to claim 1 , wherein
the anti-PD-1 antibody is any one selected from the group consisting of pembrolizumab, nivolumab, cemiplimab, JTX-4014, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, INCMGA00012, AMP-224, and AMP-514; and
the anti-PD-L1 antibody is any one selected from the group consisting of atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170, and BMS-986189.