Compositions, combinations and related methods for photoimmunotherapy

Abstract

Provided herein are conjugates, compositions and methods for use in photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds a protein on cell, for example, an IR700-antibody conjugate. In some embodiments, the phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. Features of the conjugates, compositions and methods, including the dose of the conjugate, provide various advantages, such as lower toxicity and/or improved efficacy. In some embodiments, also provided is a dual label phthalocyanine-dye conjugate in which the targeting molecule is conjugated to an additional fluorescent dye, which can be used for photoimmunotherapy while, for example, also exhibiting improved performance for imaging or detection. Also provided are therapeutic methods using the conjugates and compositions for treatment of diseases and conditions, including tumors or cancers.

1 .- 208 . (canceled) 
     
     
         209 . A method of treating a lesion in a subject by photoimmunotherapy, the method comprising:
 (a) intravenously administering an immune checkpoint inhibitor to the subject;   (b) intravenously administering to the subject a conjugate comprising IR700 linked to an anti-CD25 antibody, wherein the conjugate is administered in an amount that is between at or about 0.25 mg/kg and at or about 10 mg/kg;   (c) after administering the conjugate, irradiating the lesion at a wavelength of 600 nm to 850 nm at a dose of from at or about 25 J cm −2  to at or about 400 J cm −2  or from at or about 25 J/cm fiber length to at or about 500 J/cm fiber length.   
     
     
         210 . The method of  claim 209 , wherein the immune checkpoint inhibitor is administered at least 48 hours before the irradiating step. 
     
     
         211 . The method of  claim 209 , wherein the immune checkpoint inhibitor is administered at least 72 hours before the irradiating step. 
     
     
         212 . The method of  claim 209 , wherein the immune checkpoint inhibitor is administered at least 1 week prior to the irradiating step. 
     
     
         213 . The method of  claim 209 , wherein the irradiation is carried out between 30 minutes and 96 hours after administering the conjugate. 
     
     
         214 . The method of  claim 209 , wherein the irradiation is carried out 24 hours±3 hours after administering the conjugate. 
     
     
         215 . The method of  claim 209 , wherein the conjugate is administered in an amount that is between at or about 0.25 mg/kg and at or about 7.5 mg/kg. 
     
     
         216 . The method of  claim 209 , wherein the conjugate is administered in an amount that is between at or about 0.25 mg/kg and at or about 5.0 mg/kg. 
     
     
         217 . The method of  claim 209 , wherein the conjugate is administered in an amount that is between at or about 0.25 mg/kg and at or about 2.0 mg/kg. 
     
     
         218 . The method of  claim 209 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody. 
     
     
         219 . The method of  claim 218 , wherein the anti-PD-1 antibody is selected from among nivolumab pembrolizumab, pidilizumab, lambrolizumab, AMP-224, and antigen-binding fragments of any of the foregoing. 
     
     
         220 . The method of  claim 209 , wherein the anti-CD25 antibody is basiliximab or an antigen-binding fragment thereof or daclizumab or an antigen-binding fragment thereof. 
     
     
         221 . The method of  claim 209 , wherein the anti-CD25 antibody is basiliximab. 
     
     
         222 . The method of  claim 210 , comprising continued administration of the immune checkpoint inhibitor subsequent to the irradiating step. 
     
     
         223 . The method of  claim 222 , wherein the administration of the immune checkpoint inhibitor is repeated once a week, once every two weeks, once every three weeks or once a month during the dosing schedule. 
     
     
         224 . The method of  claim 209 , wherein the irradiating step is carried out at a wavelength of 690±50 nm or at a wavelength of 690±20 nm. 
     
     
         225 . The method of  claim 209 , wherein the irradiating step is carried out at a dose of at or about 50 J cm −2  or at or about 100 J/cm of fiber length. 
     
     
         226 . The method of  claim 209 , further comprising a dosing schedule whereby steps (b) and (c) are repeated. 
     
     
         227 . The method of  claim 226 , wherein steps (b) and (c) are repeated if a residual tumor remains at a time that is more than or about 2 weeks, 3 weeks, 4 weeks, 2 months, 6 months or 1 year after initiation of the prior administration of the conjugate. 
     
     
         228 . The method of  claim 209 , wherein the lesion is a tumor and the tumor is a superficial tumor. 
     
     
         229 . The method of  claim 228 , wherein the irradiating step comprises illuminating the superficial tumor with a microlens-tipped fiber for surface illumination. 
     
     
         230 . The method of  claim 209 , wherein the lesion is a tumor and the tumor is an interstitial tumor or a subcutaneous tumor. 
     
     
         231 . The method of  claim 230 , wherein the irradiating step is carried out using one or more cylindrical diffusing fibers. 
     
     
         232 . The method of  claim 209 , wherein the lesion is a tumor that is associated with a head or neck cancer. 
     
     
         233 . The method of  claim 232 , wherein the head or neck cancer is head and neck squamous cell carcinoma (HNSCC). 
     
     
         234 . The method of  claim 209 , wherein the lesion is a tumor that is a cutaneous squamous cell carcinoma (cuSCC).