Methods and compositions for targeting t-cell cancers

Abstract

Described herein are compositions of binding agents and carrier proteins, and at least one therapeutic agent, wherein the binding agents are capable of binding an antigen expressed on T-cells and methods of making and using the same, in particular, as a T-cell cancer therapeutic. Also described are lyophilized compositions of binding agents and carrier proteins, and at least one therapeutic agent, and methods of making and using the same, in particular, as a T-cell cancer therapeutic.

1 - 54 . (canceled) 
     
     
         55 . A method for treating T-cell cancer cells, comprising contacting the cancer cells with an effective amount of a nanoparticle composition, said nanoparticle composition maintained in contact with said cells for a sufficient period of time to treat the cancer cells, wherein said nanoparticle composition comprises nanoparticles having an outer surface, each of said nanoparticles comprising:
 (a) a carrier protein,   (b) a binding agent with a T-cell antigen-binding portion, and   (c) a therapeutically effective amount of paclitaxel;   wherein the antigen-binding portion of said binding agents are capable of binding to a T-cell antigen in vivo.   
     
     
         56 . The method of  claim 55 , wherein the nanoparticle comprises about 100 to about 1000 binding agents. 
     
     
         57 . The method of  claim 55 , wherein the antigen-binding portion binds to T-cell receptor (TCR). 
     
     
         58 . The method of  claim 55 , wherein the antigen-binding portion binds to an antigen selected from CD2, CD3, CD4, CD5, CD8, CD25, CD30, CD40, CD52, CD 122, or CCR4. 
     
     
         59 . The method of  claim 58 , wherein the antigen is CD2 or CD3. 
     
     
         60 . The method of  claim 55 , wherein the nanoparticle composition is a lyophilized nanoparticle composition that is reconstituted in an aqueous solution prior to administration. 
     
     
         61 . The method of  claim 55 , wherein the composition is stable at about 20° C. to about 25° C. for up to about 12 months or longer. 
     
     
         62 . The method of  claim 55 , wherein the binding agent comprises Slipizumab, OKT3, Leu 55, Zanolimumab, Zanolimumab, Brentuximab vedotin, Mik-β1, KW-0761, or a combination thereof. 
     
     
         63 . The method of  claim 55 , wherein the binding agent is muromonab-CD3 (OKT3). 
     
     
         64 . The method of  claim 55 , wherein the antigen binding portion is an aptamer, a receptor ligand, or an Fab fragment. 
     
     
         65 . The method of  claim 55 , wherein the composition comprises one or more additional cancer therapeutic agents. 
     
     
         66 . The method of  claim 65 , wherein the additional cancer therapeutic agent is selected from abiraterone, bendamustine, bortezomib, carboplatin, cabazitaxel, cisplatin, chlorambucil, dasatinib, docetaxel, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, gefitinib, idarubicin, imatinib, hydroxyurea, imatinib, lapatinib, leuprorelin, melphalan, methotrexate, mitoxantrone, nedaplatin, nilotinib, oxaliplatin, paclitaxel, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, or cyclophosphamide. 
     
     
         67 . The method of  claim 55 , wherein fewer than about 50% of said nanoparticles are oligomeric 
     
     
         68 . The method of  claim 55 , wherein less 40% of the nanoparticles present in said composition are oligomeric. 
     
     
         69 . The method of  claim 55 , wherein less than 30% of the nanoparticles present in said composition are oligomeric. 
     
     
         70 . The method of  claim 55 , wherein less than 20% of the nanoparticles present in said composition are oligomeric. 
     
     
         71 . The method of  claim 55 , wherein less than 10% of the nanoparticles present in said composition are oligomeric. 
     
     
         72 . The method of any one of  claim 55 , wherein less than 5% of the nanoparticles present in said composition are oligomeric. 
     
     
         73 . The method of  claim 55 , wherein the average size of the nanoparticles is between 90 nm and 800 nm. 
     
     
         74 . The method of  claim 55 , wherein the average size of the nanoparticles is between about 90 nm and about 160 nm. 
     
     
         75 . The method of  claim 55 , wherein the carrier protein comprises albumin, gelatin, elastin, gliadin, legumin, zein, a soy protein, a milk protein, a whey protein, or a combination thereof. 
     
     
         76 . The method of  claim 75 , wherein the carrier protein is albumin. 
     
     
         77 . The method of  claim 76 , wherein the albumin is human serum albumin. 
     
     
         78 . The method of  claim 76 , the albumin is recombinant human serum albumin. 
     
     
         79 . The method of  claim 55 , wherein the composition is formulated for intravenous delivery. 
     
     
         80 . The method of  claim 55 , wherein the nanoparticles have a dissociation constant between about 1×10 −11  M and about 1×10 −8  M. 
     
     
         81 . The method of  claim 55 , wherein the therapeutically effective amount of the nanoparticle composition comprises about 75 mg/m 2  to about 175 mg/m 2  paclitaxel. 
     
     
         82 . The method of  claim 55 , wherein the T-cell cancer comprises peripheral T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic lymphoma cutaneous T-cell lymphoma, Adult T-cell Leukemia/Lymphoma (ATLL), enteropathy-type T-cell lymphoma, hematosplenic gamma-delta T-cell lymphoma, blastic K-cell lymphoma, lymphoblastic lymphoma, nasal K/T-cell lymphoma, treatment-related T-cell lymphoma, or a combination thereof. 
     
     
         83 . The method of  claim 55 , wherein the T-cell cancer is T-cell lymphoma.