Compositions comprising and methods of using dendritic cell exosomes
AssigneeBaylor College of Medicine
InventorsWillliam K. DECKER, Damilola OYEWOLE-SAID, Vanaja KONDURI, Nalini BISHT, Keenan ERNSTE, Matthew M. HALPERT
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Abstract
Provided herein are methods to generate extracellular vesicles (EV) from large cultures of polarized DC as well as additional procedures to separate CTLA-4+ and CTLA-4neg EV from each other and recover both populations of EV in a state that is physically and functionally intact, and as well as compositions comprising the EV obtained by the methods. Also provided are the use of CTLA-4neg EV for the treatment of cancer, and the use of CTLA-4+ EV for the treatment of GVHD and other T-cell mediated autoimmune conditions.
Claims44
A method of generating extracellular vesicles (EV) from dendritic cells (DC), the method comprising (i) maturing DC towards either TH1 polarization or TH2 polarization, and (ii) isolating EV secreted by the polarized DC.
A method of separating CTLA-4+ and CTLA-4neg EV from each other to recover both populations of EV in a state that is physically and functionally intact, the method comprising isolating EV from mature DC cell culture supernatant using PEG precipitation and extracting the CTLA-4+ EV using bead-bound anti-CTLA-4 antibody, thereby separating CTLA-4+ and CTLA-4neg EV from each other.
A method of inducing adaptive TH1 polarization and activation of T cells, comprising contacting the T cells with CTLA-4neg DC-derived EV.
A method of treating a disease in a patient in need thereof, the method comprising administering CTLA-4neg DC-derived EV to the patient.
A method of inhibiting adaptive TH1 polarization and activation of CD8+ T cells, the method comprising contacting the T cells with CTLA-4+ DC-derived EV.
A method of treating an autoimmune condition in a patient, the method comprising administering CTLA-4+ DC-derived EV to the patient.
Dependencies are inferred from the claim text.