Compositions and methods for delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse

Abstract

The present disclosure provides compositions and methods for the delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse. The compositions comprise (i) a structure comprising an injectable polymer or scaffold comprising pores; (ii) lymphocytes disposed within the structure, (iii) at least one lymphocyte-adhesion moiety associated with the structure; and (iv) at least one lymphocyte-activating moiety associated with the structure, and optionally an immune stimulant.

1 - 42 . (canceled) 
     
     
         43 . An alginate polymer scaffold coated with a synthetic collagen-mimetic peptide wherein at the time of administration to a subject the scaffold houses: (i) tumor-reactive T lymphocytes; and (ii) porous silica microparticles (a) coated with anti-CD3/CD28 antibodies and (b) loaded with interleukin 15. 
     
     
         44 . A composition comprising at the time of administration to a subject (i) a structure comprising an injectable polymer or an implantable polymer scaffold comprising pores; (ii) lymphocytes, (iii) at least one lymphocyte-adhesion moiety; and (iv) at least one lymphocyte-activating moiety. 
     
     
         45 . A composition of  claim 44 , wherein the lymphocytes are T-cells and/or natural killer cells. 
     
     
         46 . A composition of  claim 44 , wherein the lymphocyte-activating moieties are bound to or incorporated in one or more particles. 
     
     
         47 . A composition of  claim 44 , wherein the lymphocyte-activating moiety comprises antibodies specific for CD3, CD28, and/or CD137. 
     
     
         48 . A composition of  claim 44 , further comprising an immune stimulant. 
     
     
         49 . A composition of  claim 48 , wherein the immune stimulant is a cytokine, an antibody, a small molecule, and/or a vaccine adjuvant. 
     
     
         50 . A composition of  claim 44 , wherein the structure is injectable. 
     
     
         51 . A composition of  claim 44 , wherein the lymphocyte-adhesion moieties and/or lymphocyte-activating moieties are associated with the structure in a bioactive coating on the scaffold. 
     
     
         52 . A composition of  claim 44 , wherein the lymphocyte-activating moieties are associated with particles embedded in the pores of the scaffold. 
     
     
         53 . A composition of  claim 44 , wherein the lymphocyte-activating moieties are associated with particles attached to the surface of the scaffold or are embedded in the scaffold. 
     
     
         54 . A method of treating a tumor in a subject comprising implanting a composition of  claim 43  into a subject within a proximity to a tumor cell sufficient to lead to the destruction of the tumor cell in the subject, thereby treating the tumor. 
     
     
         55 . A method of  claim 54 , wherein the implanting is within a tumor resection bed. 
     
     
         56 . A method of  claim 54 , wherein the implanting leads to the destruction of a tumor cell of an incompletely resected tumor or a tumor cell of a metastasized tumor. 
     
     
         57 . A method of reducing surgical treatment failure caused by metastatic relapse after resection of a primary tumor, comprising administering a composition of  claim 43  to a tumor resection bed of a subject thereby reducing surgical treatment failure caused by metastatic relapse after primary tumor resection. 
     
     
         58 . A method of treating a tumor in a subject comprising implanting a composition of  claim 44  into a subject within a proximity to a tumor cell sufficient to lead to the destruction of the tumor cell in the subject, thereby treating the tumor. 
     
     
         59 . A method of  claim 58 , wherein the implanting is within a tumor resection bed. 
     
     
         60 . A method of  claim 58 , wherein the implanting leads to the destruction of a tumor cell of an incompletely resected tumor or a tumor cell of a metastasized tumor. 
     
     
         61 . A method of reducing surgical treatment failure caused by metastatic relapse after resection of a primary tumor, comprising administering a composition of  claim 44  to a tumor resection bed of a subject thereby reducing surgical treatment failure caused by metastatic relapse after primary tumor resection.