Platform for enhanced targeted cell delivery

Abstract

Embodiments of the disclosure concern methods and compositions for delivering therapeutic, diagnostic or interventional moieties, such as complex and simple entities such as biologics, including at least cells, for example. The methods employ targeted delivery by employing at least one ALCAM-binding moiety on the therapeutic, diagnostic or interventional moiety to be delivered. In specific cases, the ALCAM-binding moiety is present on or with the therapeutic moiety in multiple iterations. In certain embodiments, the ALCAM-binding moiety comprises at least one SRCR domain from CD6 and a stalk, such as from CD6, of the secretable or molecular form thereof.

What is claimed is: 
     
         1 . A method of providing a therapeutic moiety to an individual,
 comprising the step of delivering an effective amount of a therapeutic composition to the individual, said composition comprising a) at least one therapeutic moiety; said moiety operably linked to b) adhesion molecule binding moiety, or   comprising the step of delivering an effective amount of cells comprising the therapeutic composition.   
     
     
         2 . The method of  claim 1 , wherein the individual is in need of therapy that targets desired particular cell(s) or tissue(s) comprising particular cell(s) in the individual. 
     
     
         3 . The method of  claim 2 , wherein the particular cells are ALCAM-expressing pathological endothelial cells. 
     
     
         4 . The method of  claim 3 , wherein the ALCAM-expressing pathological endothelial cells are within the blood-brain barrier. 
     
     
         5 . The method of  claim 1 , wherein the individual has a medical condition selected from the group consisting of cancer, pathogen infection, experimental autoimmune encephalomyelitis, brain abscess, epilepsy, multiple sclerosis, Alzheimer's Disease, cerebral edema, cerebral ischemia, prion diseases, encephalitis, or inflammation. 
     
     
         6 . The method of  claim 1 , wherein the adhesion molecule binding moiety comprises an activated leukocyte adhesion molecule (ALCAM)-binding moiety, wherein the ALCAM-binding moiety comprises at least one D3 region of the cluster of differentiation 6 (CD6) scavenger receptor cysteine rich (SRCR) domain and at least one CD6 stalk domain 
     
     
         7 . The method of  claim 1 , wherein the composition comprises 1, 2, 3, 4, 5, or more ALCAM-binding moieties. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic moiety comprises a cell, cell derivative, small molecule, protein, peptide, nucleic acid, viral genome or coat, exosomes, dendrimers, biomimic nanoparticles, micelles, liposomes, or combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the adhesion molecule binding moiety comprises a secretable form of minimal binding element [MBE] n  CD6 D3 or the multiplicity thereof. 
     
     
         10 . The method of  claim 1 , wherein the cell is an immune cell, stem cell, mesenchymal stromal cell (MSC), or hybridoma. 
     
     
         11 . The method of  claim 10 , wherein the immune cell is a T cell, NK cell, NK T cell, B cell, Th17, dendritic cell, or T regulatory cell. 
     
     
         12 . The method of  claim 10 , wherein the stem cell is hematopoietic stem cell or mesenchymal stem cell. 
     
     
         13 . The method of  claim 8 , wherein the cell derivative is a corpuscle or microsome. 
     
     
         14 . The method of  claim 1 , wherein the ALCAM-binding moiety is configured as at least part of an ectodomain of a cell receptor or an adhesion molecule. 
     
     
         15 . The method of  claim 14 , wherein the cell receptor comprises a transmembrane domain and at least one endodomain. 
     
     
         16 . The method of  claim 15 , wherein the endodomain is an ALCAM ligand (CD6 or any other molecule) endodomain. 
     
     
         17 . The method of  claim 15 , wherein the endodomain is truncated or mutated. 
     
     
         18 . The method of  claim 14 , wherein the receptor lacks an endodomain. 
     
     
         19 . The method of  claim 14 , wherein the receptor is a chimeric antigen receptor, a chimeric cytokine receptor, αβT cell receptor, a chemokine receptor, or any other anchoring protein. 
     
     
         20 . The method of  claim 1 , wherein the adhesion molecule binding moiety is a binding moiety for ALCAM, ICAM-1, JAM-1, VCAM-1, Addressin, GLYCAM-1, or a selectin. 
     
     
         21 . The method of  claim 20 , wherein the binding moiety for ICAM-1 comprises part or all of MAC-1 and/or part or all of LFA-1. 
     
     
         22 . The method of  claim 20 , wherein the binding moiety for JAM-1 comprises part or al of MAC-1 and/or part or all of LFA-1. 
     
     
         23 . The method of  claim 20 , wherein the binding moiety for VCAM-1 comprises part or all of VLA-4. 
     
     
         24 . The method of  claim 20 , wherein the binding moiety for GLYCAM-1 comprises part or all of LPAM-1. 
     
     
         25 . The method of  claim 20 , wherein the binding moiety for Addressin comprises part or all of LPAM-1. 
     
     
         26 . The method of  claim 20 , wherein the binding moiety for the selectins comprises a minimal lectin domain.