RADIOACTIVE ANTITUMOR AGENT

1 . A radioactive antitumor agent comprising a 225 Ac-labeled anti-MUC5AC humanized antibody (humanized antibody labeled with actinium-225 that specifically binds to mucin subtype 5AC) as an active ingredient, which is used in combination with a drug for reducing renal toxicity.

2 . A radioactive antitumor agent comprising a 225 Ac-labeled anti-MUC5AC humanized antibody (humanized antibody labeled with actinium-225 that specifically binds to mucin subtype 5AC) and a drug for reducing renal toxicity as active ingredients.

3 . The radioactive antitumor agent according to claim 1 , wherein the drug for reducing renal toxicity is a drug for reducing renal toxicity caused by the administration of a drug containing Actinium-225.

4 . The radioactive antitumor agent according to claim 1 , wherein the drug for reducing renal toxicity is a drug for reducing renal toxicity caused by Actinium-225 or a daughter nuclide of Actinium-225.

5 . The radioactive antitumor agent according to claim 1 , wherein the aforementioned renal toxicity is late renal toxicity that occurs after a lapse of not less than 10 weeks after administration of the aforementioned radioactive antitumor agent.

6 . The radioactive antitumor agent according to claim 1 , wherein the aforementioned drug for reducing renal toxicity is a diuretic or a metal scavenger.

7 . The radioactive antitumor agent according to claim 6 , wherein the aforementioned metal scavenger comprises DTPA, Ca-DTPA, or Zn-DTPA.

8 . The radioactive antitumor agent according to claim 6 , wherein the aforementioned diuretic comprises furosemide, spironolactone, or eplerenone.

9 . The radioactive antitumor agent according to claim 1 , wherein the aforementioned anti-MUC5AC humanized antibody comprises

a heavy chain variable region consisting of

(1) the amino acid sequence shown in SEQ ID NO: 1 (H01), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 1;

(2) the amino acid sequence shown in SEQ ID NO: 2 (H02), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 2;

(3) the amino acid sequence shown in SEQ ID NO: 3 (H03), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 3; or

(4) the amino acid sequence shown in SEQ ID NO: 4 (H04), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 4; and

a light chain variable region consisting of

(5) the amino acid sequence shown in SEQ ID NO: 5 (L01), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 5;

(6) the amino acid sequence shown in SEQ ID NO: 6 (L02), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 6;

(7) the amino acid sequence shown in SEQ ID NO: 7 (L03), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 7; or

(8) the amino acid sequence shown in SEQ ID NO: 8 (L04), or an amino acid sequence having not less than 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 8.

10 . The radioactive antitumor agent according to claim 1 , wherein the aforementioned anti-MUC5AC humanized antibody is a humanized antibody having

(1) a heavy chain variable region consisting of the amino acid sequence shown by SEQ ID NO: 1 (H01) or an amino acid sequence having 95% or more sequence identity with the amino acid sequence shown by SEQ ID NO: 1, and

(7) a light chain variable region consisting of the amino acid sequence shown by SEQ ID NO: 7 (L03) or an amino acid sequence having 95% or more sequence identity with the amino acid sequence shown by SEQ ID NO: 7.

11 . The radioactive antitumor agent according to claim 1 , wherein the aforementioned 225 Ac-labeled anti-MUC5AC humanized antibody is a conjugate of a chelating agent complexed with actinium-225 and the aforementioned anti-MUC5AC humanized antibody, and the Fc region of the aforementioned anti-MUC5AC humanized antibody is site-specifically modified with the aforementioned chelating agent via a linker.

12 . The radioactive antitumor agent according to claim 11 , wherein the aforementioned linker comprises a peptide represented by the following formula (i) which consists of not less than 13 and not more than 17 amino acid residues, and which is formed by a crosslinking reaction of the aforementioned peptide modified by a crosslinking agent and the aforementioned antibody:

(Xa)-Xaa1-(Xb)-Xaa2-(Xc)-Xaa3-(Xd)  (i)

wherein Xa, Xb, Xc and Xd are continuous X in the number of a, continuous X in the number of b, continuous X in the number of c, and continuous X in the number of d, respectively,

X is an amino acid residue having neither a thiol group nor a haloacetyl group in the side chain,

a, b, c and d are each independently an integer of not less than one and not more than 5, and satisfy a+b+c+d≤14,

Xaa1 and Xaa3 are each independently an amino acid residue derived from an amino acid having a thiol group in the side chain, or

one is an amino acid residue derived from an amino acid having a thiol group in the side chain and the other is an amino acid residue derived from an amino acid having a haloacetyl group in the side chain, and Xaa1 and Xaa3 are linked, and

Xaa2 is a lysine residue, an arginine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, or diamino propionic acid, and modified with the aforementioned crosslinking agent.

13 . The radioactive antitumor agent according to claim 11 , wherein the aforementioned chelating agent has a structure derived from a compound represented by the following formula (A) or a salt thereof:

wherein in the formula (A), R 11 , R 13 and R 14 are each independently a group consisting of —(CH 2 ) p COOH, —(CH 2 ) p C 5 H 5 N, —(CH 2 ) p PO 3 H 2 , —(CH 2 ) p CONH 2 or —(CHCOOH)(CH 2 ) p COOH, one of R 12 and R 15 is a hydrogen atom, a carboxyl group, or a carboxyalkyl group having 2 or 3 carbon atoms, the other is a substituent for conjugating with the antibody, p is an integer of not less than 0 and not more than 3, R 15 is a hydrogen atom when R 12 is a substituent for conjugating with the antibody, and R 15 is a substituent for conjugating with the antibody when R 12 is not a substituent for conjugating with the antibody.

14 . The radioactive antitumor agent according to claim 1 , which is used to treat pancreatic cancer, thyroid cancer, liver cancer, colorectal cancer, stomach cancer, urothelial cancer, breast cancer, cervical cancer, ovarian cancer, endometrial cancer or bile duct cancer.

15 . A drug for reducing renal toxicity, which is used in combination with a radioactive antitumor agent comprising 225 Ac-labeled anti-MUCSAC humanized antibody as an active ingredient.

16 . The drug according to claim 15 , wherein the drug for reducing renal toxicity is a diuretic or a metal scavenger.

17 . A combination drug comprising a radioactive antitumor agent comprising a 225 Ac-labeled anti-MUCSAC humanized antibody as an active ingredient, and a drug for reducing renal toxicity.