Use of anti-CD47 agents to enhance immunization
Methods are provided for enhancing immunization strategies by manipulation, e.g. in vitro manipulation, of phagocytic antigen presenting cells. In the methods of the invention, phagocytic antigen presenting cells (phAPC) are incubated with a particulate antigen in the presence of an anti-CD47 agent in a dose and for a period of time sufficient to allow the phAPC to phagocytose the particulate antigen, which process generates a “loaded” phAPC. The loaded phAPC is contacted with a population of T cells matched for at least one major histocompatibility locus with the phAPC, where the T cells are stimulated after contacting to generate an effector response against an epitope or epitopes present on the particulate antigen.
1. A method of inducing a CD8+ T cell immune response to a mammalian target cell, the method comprising:
(a) contacting in vitro
(i) a phagocytic antigen presenting cell (phAPC) population comprising one or both of mammalian macrophages and dendritic cells,
(ii) the mammalian target cell,
(iii) in the presence of an effective dose of an anti-CD47 agent that blocks the interaction between CD47 and SIRPα, selected from: an antibody that binds to CD47, an antibody that binds to SIRPα, a soluble SIRPα-binding CD47 fragment, and a soluble CD47-binding SIRPαfragment; to generate a loaded phAPC population; and
(b) contacting a CD8 + T cell population with the loaded phAPC population;
wherein the CD8 + T cell population generates a response specific to the mammalian target cell.
2. The method of claim 1 , wherein the CD8+ T cell population is selectively induced to respond to the mammalian target cell.
3. The method of claim 2 , wherein the CD8 + T cell population is a human T cell population.
4. The method of claim 1 , wherein the mammalian target cell is a human cancer cell.