Compositions for reprogramming cells into dendritic cells or antigen presenting cells, methods and uses thereof

Abstract

The present disclosure relates to compositions, nucleic acid constructs, methods and kits thereof for cell induction or reprogramming cells to the dendritic cell state or antigen presenting cell state, based, in part, on the surprisingly effect described herein of novel use and combinations of transcription factors that permit induction or reprogramming of differentiated or undifferentiated cells into dendritic cells or antigen presenting cells. Such compositions, nucleic acid constructs, methods and kits can be used for inducing dendritic cells in vitro, ex vivo, or in vivo, and these induced dendritic cells or antigen presenting cells can be used for immunotherapy applications.

1 .- 49 . (canceled) 
     
     
         50 . A construct or vector comprising a combination of at least two polynucleotide sequences encoding at least two transcription factors selected from the group consisting of: BATF3, IRF8 and PU.1. 
     
     
         51 . The construct or vector according to  claim 50 , wherein the at least two transcription factors are encoded by a sequence at least 90% identical to a sequence selected from the group consisting of:
 i. SEQ. ID. 1 or SEQ. ID. 2 (BATF3),   ii. SEQ. ID. 5 or SEQ. ID. 6 (IRF8), and   iii. SEQ. ID. 7 or SEQ. ID. 8 (PU.1).   
     
     
         52 . The construct or vector according to  claim 50 , wherein the at least two transcription factors are encoded by a sequence at least 95%, identical to a sequence selected from the group consisting of:
 i. SEQ. ID. 1 or SEQ. ID. 2 (BATF3),   ii. SEQ. ID. 5 or SEQ. ID. 6 (IRF8), and   iii. SEQ. ID. 7 or SEQ. ID. 8 (PU.1).   
     
     
         53 . The construct or vector according to  claim 50 , wherein the at least two transcription factors are BATF3 and PU.1, or IRF8 and PU.1. 
     
     
         54 . The construct or vector according to  claim 50 , wherein the construct comprises at least three transcription factors, wherein said three transcription factors are in the following sequential order from 5′ to 3′:
 PU.1, IRF8, BATF3; or 
 IRF8, PU.1, BATF3. 
 
     
     
         55 . The construct or vector according to  claim 50 , wherein the vector is a viral vector. 
     
     
         56 . The construct or vector according to  claim 55 , wherein the viral vector is selected from the group consisting of: lentiviral, adeno-associated viral, adenoviral, retroviral, herpes viral, and pox viral vector. 
     
     
         57 . The construct or vector according to  claim 50 , wherein the transcription factors sequences are operably linked to a promoter region capable of controlling the transcription of said transcription factors. 
     
     
         58 . The construct or vector according to  claim 57 , wherein the promoter region comprises the tetracycline operator and a minimal cytomegalovirus (CMV) promoter or the constitutively active human ubiquitin C promoter (UbC). 
     
     
         59 . A pharmaceutical composition comprising a combination of at least two isolated transcription factors encoded by a sequence at least 90% identical to a sequence selected from a list consisting of: BATF3 (SEQ. ID. 1 or SEQ. ID. 2), IRF8 (SEQ. ID. 5 or SEQ. ID. 6), PU.1 (SEQ. ID. 7 or SEQ. ID. 8), and mixtures thereof, and
 one or more pharmaceutically acceptable excipients and/or carriers.   
     
     
         60 . The pharmaceutical composition according to  claim 59  comprising a combination of at least two isolated transcription factors encoded by a sequence at least 95% identical to a sequence from a list consisting of selected from a list consisting of: BATF3 (SEQ. ID. 1 or SEQ. ID. 2), IRF8 (SEQ. ID. 5 or SEQ. ID. 6), PU.1 (SEQ. ID. 7 or SEQ. ID. 8), and mixtures thereof. 
     
     
         61 . The pharmaceutical composition according to  claim 59  wherein the combination of isolated transcription factors is selected from the following encoded combinations:
 BATF3 (SEQ. ID. 1 or SEQ. ID. 2), IRF8 (SEQ. ID. 5 or SEQ. ID. 6) and PU.1 (SEQ. ID. 7 or SEQ. ID. 8); or BATF3 (SEQ. ID. 1 or SEQ. ID. 2) and IRF8 (SEQ. ID. 5 or SEQ. ID. 6); or IRF8 (SEQ. ID. 5 or SEQ. ID. 6) and PU.1 (SEQ. ID. 7 or SEQ. ID. 8); or BATF3 (SEQ. ID. 1 or SEQ. ID. 2) and PU.1 (SEQ. ID. 7 or SEQ. ID. 8). 
 
     
     
         62 . The pharmaceutical composition according to  claim 59 , wherein the combination of isolated transcription factors is the encoded combination of BATF3 (SEQ. ID. 1 or SEQ. ID. 2), IRF8 (SEQ. ID. 5 or SEQ. ID. 6) and PU.1 (SEQ. ID. 7 or SEQ. ID. 8). 
     
     
         63 . The pharmaceutical composition according to  claim 59 , further comprising at least one polynucleotide encoding an agent selected from the group consisting of: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-18, IL-19, IL-20, IFN-α, IFN-β, IFN-γ, TNF, TGF-β, G-CSF, M-CSF, GM-CSF, Flt-3 ligand, kit ligand, and mixtures thereof. 
     
     
         64 . A method of treatment of cancer, the method comprising administering to a patient in need thereof the construct or vector according to  claim 50 . 
     
     
         65 . The method of treatment according to  claim 64 , wherein the cancer is selected from the group consisting of: benign tumor, malignant tumor, early cancer, basal cell carcinoma, cervical dysplasia, soft tissue sarcoma, germ cell tumor, retinoblastoma, Hodgkin's lymphoma, blood cancer, prostate cancer, ovarian cancer, cervix cancer, uterus cancer, vaginal cancer, breast cancer, naso-pharynx cancer, trachea cancer, larynx cancer, bronchi cancer, bronchioles cancer, lung cancer, hollow organs cancer, esophagus cancer, stomach cancer, bile duct cancer, intestine cancer, colon cancer, colorectal cancer, rectum cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gall bladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, pancreatic cancer, leukemia, skin cancer, and myeloma.