225ac-labeled Anti-CDH3 antibodies

Abstract

The present invention addresses the problem of providing radiolabeled anti-CDH3 antibodies that exhibit an excellent antitumor effect, and a cancer treatment agent containing the same.　The present invention relates to anti-CDH3 antibodies labeled with 225Ac, and to a cancer treatment agent containing the same.

Description

225Ac labeled anti-CDH3 antibody

[0001] The present invention provides 225 The present invention relates to an Ac-labeled anti-CDH3 antibody and a cancer therapeutic agent containing the same.

[0002] 90 Y-labeled anti-CDH3 antibody ( 90 Y-labeled anti-CDH3 antibody) is expected to be useful as a therapeutic agent for tumors expressing CDH3 (Patent Document 1). 90 The Y-labeled anti-CDH3 antibody showed excellent antitumor effects in tests using tumor-bearing mice (Patent Document 2), and is a candidate for use as a pharmaceutical. 90 The safety and efficacy of Y-FF-21101 were evaluated in human clinical trials (Non-Patent Document 1). FF-21101 is a chimeric anti-CDH3 monoclonal antibody into which DOTA has been introduced using isothiocyanobenzyl DOTA, and the anti-CDH3 monoclonal antibody has a heavy chain with the amino acid sequence shown in SEQ ID NO: 1 and a light chain with the amino acid sequence shown in SEQ ID NO: 2.

[0003] 90 Therapeutic nuclides other than Y include: 59 Fe, 67 Cu, 89 Sr, 103 Ru, 153 Sm, 165 Dy, 166 Ho, 177 Lu, 186 Re, 188 Re, 198 Au, 211 At, 223 Ra, 224 Ra, 226 Th, 227 Th, 230 U. 149 Tb, 212 Bi, 213 Bi, 225 Ac, 212 However, there have been no studies on the usefulness of labeling an anti-CDH3 antibody.

[0004] Patent No. 5593560 Patent No. 5380553

[0005] ​​Clinical Cancer Research, 2020 Nov 15;26(22):5830-5842.

[0006] 90 Although the Y-labeled anti-CDH3 antibody shows excellent antitumor effects, there is room for improvement in the pursuit of even higher effects. 90 It was unclear whether a radionuclide-labeled anti-CDH3 antibody could be expected to have a superior antitumor effect than a Y-labeled anti-CDH3 antibody. The present invention was made in consideration of the above circumstances, and an objective of the present invention is to provide a radionuclide-labeled anti-CDH3 antibody that exhibits a superior antitumor effect and a cancer therapeutic agent containing the same as an active ingredient.

[0007] The present inventors 225 We prepared an Ac-labeled anti-CDH3 antibody and investigated its antitumor effect. 225 Antitumor effect of Ac-labeled anti-CDH3 antibody 90 The present invention was completed based on the discovery that this antibody is significantly superior to the Y-labeled anti-CDH3 antibody.

[0008] That is, the present invention provides the following [1] to

[22] : [1] An anti-CDH3 antibody or a recombinant antibody thereof, comprising: a heavy chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO: 3, CDR2 comprising the amino acid sequence shown in SEQ ID NO: 4, and CDR3 comprising the amino acid sequence shown in SEQ ID NO: 5; and a light chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO: 6, CDR2 comprising the amino acid sequence shown in SEQ ID NO: 7, and CDR3 comprising the amino acid sequence shown in SEQ ID NO: 8. 225 Ac is bonded to 225 [2] The Ac-labeled anti-CDH3 antibody according to [1], wherein the anti-CDH3 antibody comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 9; and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 10. 225 [3] The Ac-labeled anti-CDH3 antibody according to [1] or [2], wherein the anti-CDH3 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 1; and a light chain comprising the amino acid sequence shown in SEQ ID NO: 2. 225 ​[4] An Ac-labeled anti-CDH3 antibody. [4] The anti-CDH3 antibody according to any one of [1] to [3], wherein the anti-CDH3 antibody is a monoclonal antibody produced by an antibody-producing cell having deposit number NITE BP-1040 or deposit number NITE BP-1049. 225 [5] The anti-CDH3 antibody or its recombinant antibody is fused to the above-mentioned Ac-labeled anti-CDH3 antibody via a metal chelate. 225 The compound according to [1], which is bound to Ac. 225 [6] The Ac-labeled anti-CDH3 antibody according to [5], wherein the metal chelate is DOTA. 225 [7] An Ac-labeled anti-CDH3 antibody according to [1]. 225 [8] A cancer therapeutic agent comprising an Ac-labeled anti-CDH3 antibody. [9] The cancer therapeutic agent according to [1], for use in the treatment of cancer. 225 [9] The method according to [1] for producing a cancer therapeutic agent. 225

[10] Use of an Ac-labeled anti-CDH3 antibody according to [1]. 225

[11] A method for treating cancer, comprising administering an Ac-labeled anti-CDH3 antibody.

[12] The cancer therapeutic agent according to [7], wherein the disease to be treated is pancreatic cancer.

[13] The amount administered to a human is 0.10 to 10 MBq / m 2

[13] The cancer therapeutic agent according to [7], 225

[14] The cancer therapeutic agent according to [8], wherein the specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg. 225 Ac-labeled anti-CDH3 antibody.

[15] The dose to be administered to humans is 0.10 to 10 MBq / m 2 [8], 225

[16] An Ac-labeled anti-CDH3 antibody. 225 [8] The specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg. 225

[17] The method according to [9], wherein the disease to be treated is pancreatic cancer. 225 Use of Ac-labeled anti-CDH3 antibody.

[18] The dose to humans is 0.10 to 10 MBq / m 2 [9], 225 Use of an Ac-labeled anti-CDH3 antibody.

[19] 225[9] The specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg. 225

[20] Use of an Ac-labeled anti-CDH3 antibody.

[21] The method of treatment according to

[10] , wherein the disease to be treated is pancreatic cancer.

[22] The method of treatment according to

[10] , wherein the dose to be administered to a human is 0.10 to 10 MBq / m 2

[22] The method of treatment according to

[10] , 225 The method of treatment according to

[10] , wherein the specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg.

[0009] The present invention 225 The Ac-labeled anti-CDH3 antibody exhibits excellent antitumor effects and is useful as a cancer therapeutic agent.

[0010] 225 1 shows the biodistribution of Ac-labeled FF-21101 in HPAF-II transplanted model mice. 2 shows the time course of tumor volume in the PBS-administered HPAF-II transplanted model mice. 225 FIG. 1 shows the time course of tumor volume in HPAF-II transplanted model mice in the Ac-labeled FF-21101 (0.71 MBq / kg) administration group. 225 FIG. 1 shows the time course of tumor volume in HPAF-II transplanted model mice in the Ac-labeled FF-21101 (1.07 MBq / kg) administration group. 225 1 shows the time course of tumor volume in HPAF-II transplanted model mice in the Ac-labeled FF-21101 (1.42 MBq / kg) administration group. 2 shows the weight change rate in HPAF-II transplanted model mice in the PBS administration group. 225 FIG. 1 shows the rate of change in body weight of HPAF-II transplanted model mice in the Ac-labeled FF-21101 (0.71 MBq / kg) administration group. 225 FIG. 1 shows the weight change rate of HPAF-II transplant model mice in the Ac-labeled FF-21101 (1.07 MBq / kg) administration group. 225 1 shows the weight change rate of HPAF-II transplanted model mice in the Ac-labeled FF-21101 (1.42 MBq / kg) administration group. 2 shows the time-dependent change in tumor volume of HPAF-II transplanted model mice in the PBS administration group. 901 shows the time course of tumor volume in HPAF-II transplanted model mice in the Y-labeled FF-21101 (308 MBq / kg) administration group. 2 shows the weight change rate in HPAF-II transplanted model mice in the PBS administration group. 90 FIG. 10 is a graph showing the weight change rate of HPAF-II transplant model mice in the Y-labeled FF-21101 (308 MBq / kg) administration group.

[0011] The present invention 225 Ac-labeled anti-CDH3 antibody 225 Ac is bound 225 The term "bond" used herein means one or more chemical bonds, and is intended to mean the bond of the present invention. 225 Ac-labeled anti-CDH3 antibody is an anti-CDH3 antibody. 225 It is sufficient that Ac is linked via a covalent bond and a coordinate bond. 225 The bond with Ac is a metal chelate, and the metal chelate is covalently bound to the anti-CDH3 antibody. 225 It is bonded to Ac.

[0012] The anti-CDH3 antibody used in the present invention is an anti-CDH3 antibody or a recombinant antibody thereof comprising a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 3, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 4, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 5, and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 6, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8. Among such antibodies, an anti-CDH3 antibody or a recombinant antibody thereof comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10 is preferred, and an anti-CDH3 antibody or a recombinant antibody thereof comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 2 is even more preferred. These antibodies are described in Patent Document 2 and can be produced or obtained, for example, according to the method described in Patent Document 2.

[0013] Furthermore, a preferred anti-CDH3 antibody is an antibody produced by antibody-producing cells having deposit number NITE BP-1040 or NITE BP-1049, among the anti-CDH3 antibodies described in Patent Document 2, or a recombinant antibody thereof, and particularly preferably an antibody produced by antibody-producing cells having deposit number NITE BP-1049 or a recombinant antibody thereof.

[0014] Genetically engineered antibodies can be produced using known methods. Chimeric antibodies are antibodies consisting of the heavy and light chain variable regions of a non-human mammal, such as a mouse antibody, and the heavy and light chain constant regions of a human antibody. They can be obtained by ligating DNA encoding the variable region of a mouse antibody with DNA encoding the constant region of a human antibody, incorporating the vector into an expression vector, and introducing the vector into a host for production. Humanized antibodies, also known as reshaped human antibodies, are produced by grafting the complementarity-determining regions of a non-human mammal, such as a mouse antibody, onto the complementarity-determining regions of a human antibody, and general genetic recombination techniques for such antibodies are also known. Specifically, a DNA sequence designed to link the CDRs of a mouse antibody with the framework regions of a human antibody is synthesized by PCR from several oligonucleotides engineered to have overlapping ends. The resulting DNA is ligated to DNA encoding the constant region of a human antibody, then incorporated into an expression vector, which is then introduced into a host for production. The framework regions of the human antibody that are linked via the complementarity determining regions are selected so that the complementarity determining regions form a good antigen-binding site.

[0015] Methods for producing chimeric or humanized antibodies using genetic engineering techniques are known. That is, the VH and VL sequences of a confirmed base monoclonal antibody are genetically modified, and then the antibody is chimerized or humanized by standard methods.

[0016] Used in the present invention 225Examples of metal chelates that can be bound to Ac include DOTA, CHX-DTPA, MX-DTPA, HEHA, PEPA, TETA, TEPTA, DOTPA, DOTMP, macropa, macropid, bispa2, octopa, and crown. Of these metal chelates, DOTA is preferred. Conjugation of an anti-CDH3 antibody to a metal chelate can be carried out according to the method described in Patent Document 2 or conventional methods. For example, the amino acids that constitute antibodies have various types of side chains, and metal chelates are known that incorporate substituents that can form bonds with these side chains under mild conditions. Examples of such substituents include carboxylic acids, NHS esters, TFP esters, isothiocyanates, maleimides, alkynes, and tetrazines, which bind to primary amines, thiols, azides, trans-cyclooctene, and the like of antibodies to form covalent bonds. Isothiocyanobenzyl DOTA is a widely known and widely used metal chelate having such a substituent introduced therein (Chemistry Society Reviews, 2014, 43, 260-290).

[0017] The present invention 225 The Ac-labeled anti-CDH3 antibody is a metal chelate-introduced anti-CDH3 antibody, 225 Ac can be reacted to synthesize it. 225 Ac can be obtained by known nuclear reactions and purification, but commercially available Ac can also be used. 225 Ac is available as a solid nitrate, and when reacting with an antibody, it can be dissolved in an acid or pH buffer to prepare an acidic aqueous solution. Specifically, an aqueous solution adjusted to pH 4 to 6 is added to the solution, and the metal chelate-introduced anti-CDH3 antibody and the nitrate are reacted. 225 Ac is dissolved and reacted under heating conditions of 25 to 45° C. for 15 to 120 minutes.

[0018] The present invention 225The Ac-labeled anti-CDH3 antibody is preferably an anti-CDH3 antibody or a recombinant antibody thereof, which comprises a heavy chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO: 3, CDR2 comprising the amino acid sequence shown in SEQ ID NO: 4, and CDR3 comprising the amino acid sequence shown in SEQ ID NO: 5, and a light chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO: 6, CDR2 comprising the amino acid sequence shown in SEQ ID NO: 7, and CDR3 comprising the amino acid sequence shown in SEQ ID NO: 8, via DOTA. 225 It is bound to Ac, 225 The antibody of the present invention is an Ac-labeled anti-CDH3 antibody. 225 The Ac-labeled anti-CDH3 antibody is preferably an anti-CDH3 antibody or a recombinant antibody thereof comprising a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 9 and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 10, which is synthesized via DOTA. 225 It is bound to Ac, 225 The antibody of the present invention is an Ac-labeled anti-CDH3 antibody. 225 The Ac-labeled anti-CDH3 antibody is preferably an anti-CDH3 antibody or a recombinant antibody thereof, which comprises a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 1 and a light chain comprising the amino acid sequence shown in SEQ ID NO: 2, and is synthesized via DOTA. 225 It is bound to Ac, 225 The antibody of the present invention is an Ac-labeled anti-CDH3 antibody. 225 The Ac-labeled anti-CDH3 antibody is preferably a monoclonal antibody produced by an antibody-producing cell having deposit number NITE BP-1040 or deposit number NITE BP-1049, or a recombinant antibody thereof, which is synthesized via DOTA. 225 It is bound to Ac, 225 Ac-labeled anti-CDH3 antibody.

[0019] The cancer therapeutic agent of the present invention contains, as an active ingredient, 225 Contains Ac-labeled anti-CDH3 antibody. 225 delivering Ac to tumor cells expressing CDH3; 225 Ac exerts its effects through the cell-damaging effects of the alpha rays it generates.

[0020] The target of the cancer therapeutic agent of the present invention is a tumor expressing CDH3, and the target disease is cancer. The type of cancer is not particularly limited, but examples include lung cancer, ovarian cancer, pancreatic cancer, triple-negative breast cancer, head and neck cancer, bile duct cancer, and colorectal cancer, with pancreatic cancer being particularly preferred.

[0021] The cancer therapeutic agent of the present invention comprises: 225 An effective amount of an Ac-labeled anti-CDH3 antibody can be administered to a mammal, including a human, to suppress cancer. This term has the broadest meaning, including both a preventive effect of preventing tumor development, metastasis, implantation, and recurrence, and a therapeutic effect of inhibiting tumor cell proliferation, shrinking tumors, thereby preventing tumor growth, and improving symptoms, and is not to be construed in any restrictive manner.

[0022] The cancer therapeutic agent of the present invention may contain an unlabeled anti-CDH3 antibody. This is due to the difference in the amount of substance during the reaction in which the antibody is labeled with a radionuclide. Usually, an antibody is reacted with an amount of substance that is orders of magnitude greater than the amount of substance of the radionuclide, and only a very small amount of antibody is labeled with the radionuclide. Therefore, a large amount of unlabeled antibody remains in the reaction solution, but usually it does not separate from the labeled antibody and forms part of the cancer therapeutic agent as it is. The amount of radioactivity per unit mass of the antibody is defined as specific radioactivity (MBq / μg, etc.), and can be a factor controlling the pharmacokinetics of the active ingredient. The amount of radioactivity contained in the cancer therapeutic agent of the present invention 225 The specific radioactivity of the Ac-labeled anti-CDH3 antibody may be set so as to reduce side effects while still achieving an antitumor effect, and may be, for example, 0.01 to 5.0 MBq / mg, preferably 0.1 to 3.0 MBq / mg, and particularly preferably 0.5 to 1.5 MBq / mg.

[0023] The cancer therapeutic agent of the present invention is prepared by dissolving the above-mentioned agent in an aqueous solution, preferably in physiological saline. 225An aqueous solution containing an Ac-labeled anti-CDH3 antibody can be prepared. Generally, pharmaceutically acceptable additives may be appropriately mixed. Examples of additives include stabilizers, pH adjusters, isotonicity agents, solubilizers, and chelating agents. Examples of stabilizers include gentisic acid, ascorbic acid, benzyl alcohol, povidone, and ethanol. Examples of pH adjusters include hydrochloric acid, sodium hydroxide, acetate buffer, benzoate buffer, and histidine buffer. Examples of isotonicity agents include sodium chloride and glucose. Examples of solubilizing agents include polysorbate 80. Examples of chelating agents include ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, hexaethyleneheptamine, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. These additives may be used singly or in combination of two or more. The amount of these additives to be added is not particularly limited, and may be appropriately added depending on the purpose so that the effect thereof is fully exhibited.

[0024] The cancer therapeutic agent of the present invention can be administered in the form of an injection, and is administered to patients by methods such as intravenous administration, local administration, intraperitoneal administration, and hepatic arterial injection. The administration method, dosage, and number of administrations may be appropriately selected depending on the age, weight, and symptoms of the patient. The dosage varies depending on the symptoms, weight, age, etc. of the patient, but for example, a single dosage for an adult is 0.10 to 10 MBq / m 2 is sufficient, and 1.0 to 7.0 MBq / m 2 is preferred, and 2.0 to 4.5 MBq / m 2 is particularly preferred. The results of the dosage test in mice can also be converted into the dosage for humans. The dosage in mice (MBq / kg) is set, and the Mouse K m factor (3kg / m 2 : J Basic Clin Pharm. 2016 Mar;7(2):27-31. ) to obtain the human dose (MBq / m 2 The dosage may be determined so as to obtain the optimal antitumor effect while allowing for acceptable side effects.

[0025] Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0026] Example 1 225 Preparation of Ac-labeled FF-21101] 5 mg / mL FF-21101 (FUJIFILM Diosynth Biotechnologies U.S.A., Inc.) was added to an aqueous solution (0.25 M sodium acetate, pH 5.5) containing Ac-labeled FF-21101. 225 Ac nitrate (Oak Ridge National Laboratory) was dissolved in 0.05 mol / L HCl. 225 Ac solution was added and the mixture was incubated at 45°C for 1 hour. A portion of the labeling reaction solution was sampled, and the labeling rate was confirmed using thin layer chromatography (Merck) with a 10 mmol / L DTPA / physiological saline solution as the developing solvent. The radioactivity of the peak near the origin of the strip and the entire strip development range was measured using a radiochromatography scanner, and the labeling rate was calculated using the following formula, which confirmed that it was 90% or more. In this measurement system, free 225 Ac ions are developed toward the solvent front, and the labeled product remains at the origin. Labeling rate (%) = Radioactivity near the origin / Radioactivity in the entire development range × 100

[0027] Comparative Example 1 90 Preparation of Y-labeled FF-21101] 5 mg / mL FF-21101 (FUJIFILM Diosynth Biotechnologies U.S.A., Inc.) was added to an aqueous solution (0.25 M sodium acetate, pH 5.5) containing: 90 Y solution (Eckert & Ziegler) was added and the mixture was incubated at 40°C for 15 minutes. A portion of the labeling reaction solution was sampled, and the labeling rate was confirmed using thin layer chromatography (Biodex) with a 10 mmol / L DTPA / physiological saline solution as the developing solvent. The radioactivity of the peak near the origin of the strip and the entire developing range of the strip was measured using a radiochromatography scanner, and the labeling rate was calculated using the following formula, which confirmed that it was 90% or more. In this measurement system, free 90The Y ions are developed toward the solvent front, and the labeled form remains at the origin. Labeling rate (%) = Radioactivity near the origin / Radioactivity in the entire development range × 100

[0028] Example 2 225 Confirmation of maximum tolerated dose of Ac-labeled FF-21101 in tumor-bearing mice] 5 x 10 6 Human pancreatic cancer-derived cell line HPAF-II (ATCC) was subcutaneously transplanted into the right chest of a 6-week-old BALB / cSlc-nu / nu (female) mouse. After 9 days, 225 Ac-labeled FF-21101 (administered radioactivity 1.07, 1.42, 2.13 MBq / kg, administered antibody dose 1.04 mg / kg) was administered and followed up for 18 days (n = 5 per group). Two animals in the 2.13 MBq / kg group lost less than 80% of their body weight at the time of cell transplantation or start of administration, but none in the other groups. Therefore, 1.42 MBq / kg was determined to be the maximum tolerated dose.

[0029] Example 3 225 Biodistribution of Ac-labeled FF-21101 in tumor-bearing mice] 5 x 10 6 Human pancreatic cancer-derived cell line HPAF-II (ATCC) was subcutaneously transplanted into the right chest of a 6-week-old BALB / cSlc-nu / nu (female) mouse. After 9 days, 225 Ac-labeled FF-21101 (administered radioactivity 0.71 MBq / kg, administered antibody dose 1.04 mg / kg) was administered, and blood, heart, lungs, liver, kidneys, spleen, pancreas, bone, and tumor samples were collected 5 minutes, 24, 48, 96, and 168 hours after administration, and the radioactivity concentration per unit weight (% ID / g) was calculated (n=3, except for the blood collected 5 minutes after administration, n=2).

[0030] The average (% ID / g) for each organ is shown in Table 1, and the standard deviation (% ID / g) is shown in Table 2. A graph of these results is shown in Figure 1. A high tumor accumulation rate of 45.4% ID / g was confirmed 168 hours after administration.

[0031]

[0032]

[0033] Example 4 225 Antitumor effect of Ac-labeled FF-21101 in tumor-bearing mice] 5 x 106 Human pancreatic cancer-derived cell line HPAF-II (ATCC) was subcutaneously transplanted into the right chest of a 7-week-old BALB / cSlc-nu / nu (female) mouse. After 8 days, 225 Ac-labeled FF-21101 (administered radioactivity 0.71, 1.07, 1.42 MBq / kg, administered antibody dose 1.04 mg / kg) or PBS (vehicle) was administered, and tumor volume and body weight were measured (n=5 per group). The changes in tumor volume over time are shown in Figures 2 to 5, and the changes in body weight over time are shown in Figures 6 to 9. While the tumor volume in the PBS group grew, 225 In the Ac-labeled FF-21101 group, tumor growth was suppressed up to 52 days after administration at any administered radioactivity, and no individual mice lost less than 80% of their body weight at the start of administration.

[0034] Comparative Example 2 90 Antitumor effect of Y-labeled FF-21101 in tumor-bearing mice] 5 x 10 6 Human pancreatic cancer-derived cell line HPAF-II (ATCC) was subcutaneously transplanted into the right chest of a 7-week-old BALB / cSlc-nu / nu (female) mouse. After 8 days, 90 Y-labeled FF-21101 (308 MBq / kg, 1.04 mg / kg) or PBS (vehicle) was administered, and tumor volume and body weight were measured (n=5 per group). 90 The clinical dose of Y-labeled FF-21101 is 925 MBq / m 2 (Non-Patent Document 1) was converted to mouse body weight and set. The time course of the tumor volume is shown in Figures 10 and 11, and the time course of the body weight is shown in Figures 12 and 13. The tumor volume in the PBS group grew, while 90 The Y-labeled FF-21101 group temporarily suppressed tumor growth, but a tendency for tumor regrowth was confirmed. Furthermore, no mice lost less than 80% of their body weight at the start of administration.

Claims

1. An anti-CDH3 antibody or a recombinant antibody thereof, comprising: a heavy chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO:3, CDR2 comprising the amino acid sequence shown in SEQ ID NO:4, and CDR3 comprising the amino acid sequence shown in SEQ ID NO:5; and a light chain variable region comprising CDR1 comprising the amino acid sequence shown in SEQ ID NO:6, CDR2 comprising the amino acid sequence shown in SEQ ID NO:7, and CDR3 comprising the amino acid sequence shown in SEQ ID NO:

8. 225 Ac is bonded to 225 Ac-labeled anti-CDH3 antibody.

2. The anti-CDH3 antibody according to claim 1, comprising a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:9, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:

10. 225 Ac-labeled anti-CDH3 antibody.

3. The anti-CDH3 antibody according to claim 1 or 2, comprising a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 1, and a light chain comprising the amino acid sequence shown in SEQ ID NO:

2. 225 Ac-labeled anti-CDH3 antibody.

4. The method according to any one of claims 1 to 3, wherein the anti-CDH3 antibody is a monoclonal antibody produced by an antibody-producing cell having deposit number NITE BP-1040 or deposit number NITE BP-1049. 225 Ac-labeled anti-CDH3 antibody.

5. The anti-CDH3 antibody or its recombinant antibody is linked to the 225 The compound according to claim 1, 225 Ac-labeled anti-CDH3 antibody.

6. The method of claim 5, wherein the metal chelate is DOTA. 225 Ac-labeled anti-CDH3 antibody.

7. The method according to claim 1 225 A cancer therapeutic agent comprising an Ac-labeled anti-CDH3 antibody.

8. The composition according to claim 1 for use in the treatment of cancer. 225 Ac-labeled anti-CDH3 antibody.

9. The composition according to claim 1 for the manufacture of a cancer treatment drug. 225 Use of Ac-labeled anti-CDH3 antibody.

10. The method according to claim 1 225 A method for treating cancer, comprising administering an Ac-labeled anti-CDH3 antibody.

11. The cancer therapeutic agent according to claim 7, wherein the disease to be treated is pancreatic cancer.

12. Human dose is 0.10-10MBq / m 2 The cancer therapeutic agent according to claim 7, 13. The foregoing 225 The cancer therapeutic agent according to claim 7, wherein the specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg.

14. The method according to claim 8, wherein the disease to be treated is pancreatic cancer. 225 Ac-labeled anti-CDH3 antibody.

15. Human dose is 0.10-10MBq / m 2 The compound according to claim 8, 225 Ac-labeled anti-CDH3 antibody.

16. The foregoing 225 The specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg. 225 Ac-labeled anti-CDH3 antibody.

17. The method of claim 9, wherein the disease to be treated is pancreatic cancer. 225 Use of Ac-labeled anti-CDH3 antibody.

18. Human dose is 0.10-10MBq / m 2 10. The compound according to claim 9, 225 Use of Ac-labeled anti-CDH3 antibody.

19. The foregoing 225 The specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg. 225 Use of Ac-labeled anti-CDH3 antibody.

20. The method of treatment according to claim 10, wherein the disease to be treated is pancreatic cancer.

21. Human dose is 0.10-10MBq / m 2 The method of claim 10, wherein 22. The foregoing 225 The method of claim 10, wherein the specific radioactivity of the Ac-labeled anti-CDH3 antibody is 0.01 to 5.0 MBq / mg.

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