TREATMENT OF CIRCULATING TUMOR CELLS USING AN EXTRACORPOREAL DEVICE
The present invention relates to methods and compositions for eliminating circulating tumor cells (CTCs) in a patient with or without solid tumors. In particular, the ex vivo method utilizes a photodynamic or magnetic targeting moiety that specifically binds to antigens expressed on the cell surface of CTCs.
1 . A method for inducing apoptosis and/or necrosis resulting in cell death of circulating tumor cells (CTCs) in a subject, the method comprising:
(a) administering to the subject's blood a therapeutically effective agent comprising a phthalocyanine dye conjugated to a CTC targeting moiety that specifically binds to CTCs;
(b) ex vivo irradiating the subject's blood with an appropriate excitation light in an amount to effectively induce apoptosis, necrosis or autophagy in the CTCs; and
(c) re-introducing the irradiated blood into the subject.
2 . The method of claim 1 , wherein the phthalocyanine dye is IRDye® 700DX.
3 . The method of claim 1 , wherein the targeting moiety is selected from the group consisting of an antibody or fragment thereof, nanobody, Affibody®, diabody, minibody, antigen, ligand, protein, peptide, carbohydrate, nucleic acids, and small molecule.
4 . The method of claim 1 , wherein the targeting moiety specifically binds a CTC antigen.
5 . The method of claim 1 , wherein the therapeutically effective agent is administered with an anticoagulant.
6 . The method of claim 1 , wherein ex vivo irradiating is performed using an extracorporeal device.
7 . The method of claim 1 , further comprising after step (a) removing the unbound therapeutically effective agent from the subject's blood by filtration or dialyzing.
8 . A method of extracorporeal therapy for treating cancer in a subject having circulating tumor cells (CTCs), the method comprising:
(a) intravenously administering a therapeutically effective agent comprising a phthalocyanine dye conjugated to a CTC targeting moiety that specifically binds to CTCs;
(b) ex vivo irradiating the subject's blood with an appropriate excitation light in an amount to effectively induce apoptosis, necrosis or autophagy in the CTCs; and
(c) re-introducing the irradiated blood into the subject, thereby treating cancer in the subject.
9 . The method of claim 8 , wherein the subject has undergone solid tumor resection.
10 . The method of claim 8 , wherein the phthalocyanine dye is IRDye®700DX.
11 . The method of claim 8 , wherein the targeting moiety is selected from the group consisting of an antibody or fragment thereof, nanobody, Affibody®, diabody, minibody, antigen, ligand, protein, peptide, carbohydrate, nucleic acids, and small molecule.
12 . The method of claim 8 , wherein the targeting moiety specifically binds a CTC antigen.
13 . The method of claim 8 , wherein the therapeutically effective agent is administered with an anticoagulant.
14 . The method of claim 8 , wherein step (b) and/or (c) are performed using an extracorporeal device.
15 . The method of claim 8 , further comprising after step (a) removing the unbound therapeutically effective agent from the subject's blood by filtration or dialyzing.
16 . A method of extracorporeal treatment of cancer in a subject having circulating tumor cells (CTCs), the method comprising:
(a) administering to the subject a CTC targeting agent comprising magnetic particles conjugated to a targeting moiety that specifically binds to CTCs, wherein the targeting agent and the CTCs form a complex;
(b) ex vivo separating the blood from the complex using a magnetic field in an extracorporeal device; and
(c) re-introducing the blood into the subject, thereby treating cancer in the subject.
17 . The method of claim 16 , wherein the targeting agent is introduced ex vivo by the extracorporeal device.
18 . The method of claim 16 , wherein step (a) is performed using the extracorporeal device.
19 . The method of claim 16 , wherein the subject has undergone solid tumor resection.
20 . The method of claim 16 , wherein the targeting moiety specifically binds a CTC antigen.