Use of recombinant LAG-3 or the derivatives thereof for eliciting monocyte immune response

1. A method of treating cancer in a human subject in need thereof, which comprises:

administering to the subject a chemotherapy agent, and an effective plurality of doses of a recombinant human LAG-3 protein, or a derivative thereof;

inducing a systemic increase in the number of monocytes in blood of the subject; and

eliciting a systemic monocyte-mediated immune response;

wherein the subject is treated without administration of any additional antigen; and

wherein the recombinant human LAG-3 protein comprises an extracellular region having the first, second, third and fourth immunoglobulin-like domains of a native human LAG-3 protein, and the derivative is selected from the group consisting of:

i) a fragment of the native human LAG-3 protein comprising the first and second immunoglobulin-like domains of the native human LAG-3 protein;

ii) a fragment of the native human LAG-3 protein comprising the first, second, third and fourth immunoglobulin-like domains of the native human LAG-3 protein;

iii) a mutant form of the native human LAG-3 protein, or a fragment thereof that comprises the first and second immunoglobulin-like domains of the native human LAG-3 protein, wherein the mutant comprises a substitution of an amino acid at one or more of the following positions:

a) position 73 where ARG is substituted with GLU,

b) position 75 where ARG is substituted with ALA or GLU,

c) position 76 where ARG is substituted with GLU,

iv) a variant of the native human LAG-3 protein comprising the first, second, and third immunoglobulin-like domains of the native human LAG-3 protein; and

v) a recombinant soluble human LAG-3Ig fusion protein (IMP321) comprising at least the first and second immunoglobulin-like domains of the native human LAG-3 protein fused to human IgG1 Fc; and

wherein each dose of the recombinant human LAG-3 protein or the derivative thereof is 1-30 mg of IMP321, or a molar equivalent of 1-30 mg of IMP321.

2. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered to the subject before, with, or subsequent to, the administration of the chemotherapy agent.

3. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered to the subject subsequent to the administration of the chemotherapy agent.

4. The method of claim 1 , wherein a plurality of doses of the chemotherapy agent is administered to the subject.

5. The method of claim 4 , wherein a dose of the plurality of doses of the recombinant human LAG-3 protein, or derivative thereof, is administered to the subject subsequent to administration of each dose of the chemotherapy agent.

6. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered one or two days after the administration of the chemotherapy agent.

7. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered 12 to 96 hours after the administration of the chemotherapy agent.

8. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered at least six times.

9. The method of claim 1 , wherein the recombinant human LAG-3 protein, or derivative thereof, is administered on an every-two-week schedule.

10. The method of claim 1 , wherein each dose of the effective plurality of doses of the recombinant human LAG-3 protein, or derivative thereof, is 6-30 mg of IMP321, or a molar equivalent of 6-30 mg of IMP321.

11. The method of claim 1 , wherein each dose of the effective plurality of doses of the recombinant human LAG-3 protein, or derivative thereof, is 8-25 mg of IMP321, or a molar equivalent of 8-25 mg of IMP321.

12. The method of claim 1 , wherein a dose of the effective plurality of doses of the recombinant LAG-3 protein, or derivative thereof, is administered every one to several weeks for at least 12 weeks, separated by 13-day±2 days administration-free intervals.

13. The method of claim 1 , wherein each dose of the effective plurality of doses of the recombinant LAG-3 protein, or derivative thereof, is administered by systemic administration.

14. The method of claim 1 , wherein each dose of the effective plurality of doses of the recombinant LAG-3 protein, or derivative thereof, is administered by subcutaneous or intravenous administration.

15. The method of claim 1 , wherein the chemotherapy agent is selected from the group consisting of taxanes, anthracyclines, and gemcitabine.

16. The method of claim 15 , wherein the chemotherapy agent is a taxane.

17. The method of claim 16 , wherein the chemotherapy agent is paclitaxel.