Combination of immunotherapy with local chemotherapy for the treatment of malignancies

Abstract

The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

That which is claimed: 
     
         1 . A method for the treatment of cancer comprising administering to a patient with a cancer an effective amount of a combination treatment comprising:
 (a) a locally administered chemotherapy; and   (b) an immunotherapeutic agent.   
     
     
         2 . The method of  claim 1 , wherein the cancer is a solid form of a newly diagnosed or a recurrent cancer selected from the group consisting of a blastoma, a carcinoma, a glioma, a leukemia, a lymphoma, a melanoma, a myeloma, and a sarcoma. 
     
     
         3 . The method of  claim 1 , wherein the cancer is refractory and/or metastatic. 
     
     
         4 . The method of  claim 1 , wherein the cancer is selected from the group consisting of colorectal cancer, diffuse large B-cell lymphoma, follicular lymphoma, glioblastoma, lower grade gliomas, melanoma, multiple myeloma, non-small cell lung cancer, renal cell carcinoma, urothelial bladder cancer, ovarian cystadenocarcinoma, stomach adenocarcinoma and other gastrointestinal malignancies, head and neck adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, breast adenocarcinoma, breast cancer, and pancreatic cancer. 
     
     
         5 . The method of  claim 1 , wherein the locally administered chemotherapy is formulated by loading the locally administered chemotherapy into a lipid particulate drug delivery system, a polymeric drug delivery system, or a catheter. 
     
     
         6 . The method of  claim 5 , wherein the lipid particulate drug delivery system is selected from the group consisting of a solid lipid nanoparticle, a nanostructured lipid carrier, a lipid drug conjugate-nanoparticle, a liposome, a transfersome, an ethosome, a liposphere, a niosome, a cubosome, a virosome, an iscom, a nanoemulsion, a cochleate, and a phytosome. 
     
     
         7 . The method of  claim 5 , wherein the polymeric drug delivery system is selected from the group consisting of a dendrimer, a micelle, a polymeric microsphere, a polymeric nanoparticle, and a wafer. 
     
     
         8 . The method of  claim 5 , wherein the locally administered chemotherapy comprises a BCNU implantable wafer. 
     
     
         9 . The method of  claim 5 , wherein the delivery by a catheter is selected from the group consisting of microcatheter delivery and convection enhanced delivery. 
     
     
         10 . The method of  claim 1 , wherein locally administered chemotherapy is administered intratumorally and/or within a tumor bed. 
     
     
         11 . The method of  claim 1 , wherein locally administered chemotherapy comprises injection into a solid tumor of the patient or injection or implantation into a microenvironment in which the solid tumor resides or resided. 
     
     
         12 . The method of  claim 1 , further comprising surgically removing all or a portion of the solid tumor prior to local administration of the locally administered chemotherapy. 
     
     
         13 . The method of  claim 1 , wherein the immunotherapeutic agent comprises an immune checkpoint molecule. 
     
     
         14 . The method of  claim 13 , wherein the immune checkpoint molecule inhibits an immune checkpoint receptor or a ligand for the immune checkpoint receptor. 
     
     
         15 . The method of  claim 14 , wherein the immune checkpoint receptor is PD1. 
     
     
         16 . The method of  claim 14 , wherein the immune checkpoint molecule is an anti-PD1 antibody. 
     
     
         17 . The method of  claim 16 , wherein the anti-PD1 antibody is selected from the group consisting of AMP-224, lambrolizumab, nivolumab, and pidilizumab. 
     
     
         18 . The method of  claim 14 , wherein the ligand for the immune checkpoint receptor is selected from the group consisting of PDL1 and PDL2. 
     
     
         19 . The method of  claim 18 , wherein the immune checkpoint molecule is an anti-PDL1 antibody. 
     
     
         20 . The method of  claim 19 , wherein the anti-PDL1 antibody is selected from the group consisting of BMS-936559, MEDI-4736, and MPDL3280A. 
     
     
         21 . An immunotherapeutic, non-immunosuppressive composition comprising:
 (a) a locally administered chemotherapy; and   (b) an immunotherapeutic agent.   
     
     
         22 . A kit comprising:
 (a) a locally administered chemotherapy;   (b) an immunotherapeutic agent; and   (c) a package insert or label with directions to treat a patient with a cancer by administering a combination treatment comprising the locally administered chemotherapy and the immunotherapeutic agent.