Conjugate and photoimmunotherapy
Provided is a drug useful for photoimmunotherapy. Specifically, provided is a conjugate including an antibody molecule, a particle having an average particle diameter of 100 nm or less, and a photosensitive portion. In the conjugate, the particle having an average particle diameter of 100 nm or less is linked to the antibody molecule, and at least one of the antibody molecule or the particle is bound to the photosensitive portion. The photosensitive portion is a portion showing increase of hydrophobicity when irradiated with a light beam having a wavelength of from 500 nm to 900 nm or a portion containing a phthalocyanine skeleton.
1 . A conjugate comprising:
A) an antibody molecule linked to a
a compound represented by the following formula (Ia):
where:
L represents a direct bond or a linker;
Q represents a reactive group for forming a bond to the antibody molecule or the particle;
R 2 , R 3 , R 7 , and R 8 are each independently selected from a substituted or unsubstituted alkyl and a substituted or unsubstituted aryl;
R 4 , R 5 , R 6 , R 9 , R 10 and R 11 , when present, are each independently selected from hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkanoyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkylcarbamoyl, and a chelating ligand, wherein at least one of R 4 , R 5 , R 6 , R 9 , R 10 , or R 11 contains a water-soluble group;
R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 are each independently selected from hydrogen, a halogen, a substituted or unsubstituted alkylthio, a substituted or unsubstituted alkylamino, and a substituted or unsubstituted alkoxy, or at least one of i) R 13 and R 14 , and carbon atoms to which R 13 and R 14 are bonded, ii) R 17 and R 18 , and carbon atoms to which R 17 and R 18 are bonded, or iii) R 21 and R 22 , and carbon atoms to which R 21 and R 22 are bonded, form a fused ring; and
X 2 and X 3 each independently represent a C 1 to C 10 alkylene with or without an intervening heteroatom between carbon-carbon bonds; and
B) a magnetic particle or a semiconductor particle having an average particle diameter of 100 nm or less, which is linked to the antibody molecule:
wherein at least one of the antibody molecule or the particle is linked to a portion showing increase of hydrophobicity when irradiated with a light beam having a wavelength of from 500 nm to 900 nm.
2 . The conjugate according to claim 1 , wherein the antibody molecule is linked to the portion showing increase of hydrophobicity when irradiated with a light beam having a wavelength of from 500 nm to 900 nm.
3 . The conjugate according to claim 1 , wherein the compound represented by the formula (Ia) is a compound represented by the following formula (Ib):
where:
X 1 and X 4 each independently represent a C 1 to C 10 alkylene with or without an intervening heteroatom; and
R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 16 , R 17 , R 18 , R 19 , X 2 , and X 3 are as defined in claim 1 .
4 . The conjugate according to claim 1 , wherein the compound represented by the formula (Ia) is a compound represented by the following formula (II).
5 . The conjugate according to claim 1 , wherein the magnetic particle contains iron oxide or a gadolinium compound.
6 . The conjugate according to claim 1 , wherein the semiconductor particle is a quantum dot.
7 . The conjugate according to claim 1 , wherein the average particle diameter of the particle is from 1 nm to 50 nm.
8 . The conjugate according to claim 1 , wherein the number of the antibody molecules linked to the particle is from 1 to 20 per the particle.
9 . A composition for pharmaceutical composition for photoimmunotherapy (PIT), comprising the conjugate of claim 1 .
10 . The conjugate according to claim 1 , wherein the conjugate is for use in treatment of a tumor by photoimmunotherapy.
11 . The conjugate according to claim 10 , wherein the conjugate is further for use in imaging of a tumor.
12 . The composition according to claim 9 , wherein the composition is for use in treatment of a tumor by photoimmunotherapy.
13 . The composition according to claim 12 , wherein the composition is further for use in imaging of a tumor.
14 . A method of phototherapy in a patient having a tumor, the method comprising:
irradiating the patient with a light beam having a wavelength of from 500 nm to 900 nm, wherein the patient has been previously administered the conjugate of claim 1 .
15 . The method according to claim 14 , wherein the tumor therapeutic agent is further used for imaging of a tumor.
16 . A method of treating a tumor, comprising:
administering the conjugate of claim 1 to a patient having a tumor; and
irradiating the patient with a light beam having a wavelength of from 500 nm to 900 nm.
17 . The method according to claim 16 , further comprising, before the step of irradiating the patient with the light beam, a step of imaging a tumor of the patient having administered thereto the conjugate or the composition.