Methods for photoimmunotherapy and related biomarkers
Provided are methods involving the use of biomarkers, in relation to photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds a protein on tumor cell, for example, an IR700-antibody conjugate, and combination therapies, for example, that include photoimmunotherapy and an additional therapeutic agent, such as an immune modulating agent. In some aspects, the provided embodiments can be used to identify or select subjects for photoimmunotherapy and/or the combination therapy, or to assess the likelihood of response to photoimmunotherapy and/or to the additional therapeutic agents. Features of the methods and uses provide various advantages, such as improved efficacy. In some aspects, the provided embodiments can be used to provide personalized medicine and tailored therapy regimens for subjects. Also provided are therapeutic methods involving the use of biomarkers in the treatment of diseases and conditions, including tumors or cancers.
1 . A method of treating a tumor that is a head or neck cancer in a subject, the method comprising administering to the subject a photoimmunotherapy (PIT) treatment, thereby treating the tumor,
wherein the PIT treatment comprises a conjugate comprising a silicon phthalocyanine dye and an EGFR binding molecule; and
wherein the subject has been selected for treatment by:
a) measuring in a sample from the subject a first level of an immune checkpoint biomarker comprising a PD-L1 expression;
b) comparing the first level of PD-L1 from the subject to a first threshold level of PD-L1 expression, wherein the first threshold level is a Combined Positive Score (CPS) of PD-L1 expression equal to 30; and
c) selecting the subject for treatment if the first level from the subject is lower than the first threshold level.
2 . The method of claim 1 , wherein the sample is a tumor sample, a blood sample, or a serum sample.
3 . The method of claim 1 , wherein the first threshold level is measured as a Combined Positive Score (CPS) equal to the number of cells staining positive for the immune checkpoint biomarker, divided by the total number of tumor cells, multiplied by 100.
4 . The method of claim 1 , wherein the PIT treatment comprises irradiating an area proximal to the tumor at a wavelength of at or about 660 nm to at or about 740 nm.
5 . The method of claim 1 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.
6 . The method of claim 1 , wherein the method further comprises:
measuring a second level of the immune checkpoint biomarker in a second sample from the subject after the PIT treatment;
determining whether the second level of the immune checkpoint biomarker is increased in the subject relative to the first level measured prior to the PIT treatment; and
if the second level is increased relative to the first level, administering an immune checkpoint inhibitor to the subject.
7 . The method of claim 1 , wherein the PIT treatment comprises exposing the conjugate to light that has a wavelength within a range of at or about 660 nm to at or about 740 nm.
8 . The method of claim 1 , wherein the PIT treatment comprises exposing the conjugate to light that has a wavelength of at or about 690 nm.
9 . The method of claim 1 , wherein the silicon phthalocyanine dye comprises the formula:
wherein:
L is a linker;
Q is a reactive group for attachment of the dye to the EGFR binding molecule;
R 2 , R 3 , R 7 , and R 8 are each independently selected from among substituted alkyl and substituted aryl;
R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 are each independently selected from among hydrogen, substituted alkyl, substituted alkanoyl, substituted alkoxycarbonyl, substituted alkylcarbamoyl, and a chelating ligand, wherein at least one of R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 comprises 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 among hydrogen, halogen, substituted alkylthio, substituted alkylamino and substituted alkoxy; and
X 2 and X 3 are each independently C 1 -C 10 alkylene.
10 . The method of claim 7 , wherein the silicon phthalocyanine dye is IR700.
11 . The method of claim 7 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.
12 . The method of claim 7 , wherein the silicon phthalocyanine dye comprises the formula:
wherein:
L is a linker;
Q is a reactive group for attachment of the dye to the EGFR binding molecule;
R 2 , R 3 , R 7 , and R 8 are each independently selected from among substituted alkyl and substituted aryl;
R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 are each independently selected from among hydrogen, substituted alkyl, substituted alkanoyl, substituted alkoxycarbonyl, substituted alkylcarbamoyl, and a chelating ligand, wherein at least one of R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 comprises 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 among hydrogen, halogen, substituted alkylthio, substituted alkylamino and substituted alkoxy; and
X 2 and X 3 are each independently C 1 -C 10 alkylene.
13 . The method of claim 8 , wherein the silicon phthalocyanine dye is IR700.
14 . The method of claim 8 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.
15 . The method of claim 10 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.
16 . The method of claim 12 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.
17 . The method of claim 1 , wherein the silicon phthalocyanine dye is IR700.