Methods for treating cancers and pathogen infections using antigen-presenting cells loaded with RNA

DETAILED DESCRIPTION It has now been discovered that tumor formation in a patient can be treated or prevented by administering to the patient an antigen-presenting cell(s) that is loaded with antigen encoded in RNA derived from a tumor.
For convenience, an RNA-enriched tumor preparation can be used in lieu of purified RNA.
The invention thus circumvents the need purify RNA or isolate and identify a tumor antigen.
Using similar methods and pathogen-derived RNA, pathogen infection in a patient can be treated or prevented.
The RNA-loaded antigen-presenting cells can be used to stimulate CTL proliferation ex vivo or in vivo.
The ex vivo expanded CTL can be administered to a patient in a method of adoptive immunotherapy.
Accordingly, the invention features a method for producing an RNA-loaded antigen-presenting cell (APC); the method involves introducing into an APC in vitro (i) tumor-derived RNA that includes tumor-specific RNA which encodes a cell-surface tumor antigenic epitope which induces T cell proliferation or (ii) pathogen-derived RNA that includes pathogen-specific RNA which encodes a pathogen antigenic epitope that induces T cell proliferation.
Upon introducing RNA into an APC (i.
e.
, "loading" the APC with RNA), the RNA is translated within the APC, and the resulting protein is processed by the MHC class I or class II processing and presentation pathways.
Presentation of RNA-encoded peptides begins the chain of events in which the immune system mounts a response to the presented peptides.
Preferably, the APC is a professional APC such as a dendritic cell or a macrophage.
Alternatively, any APC can be used.
For example, endothelial cells and artificially generated APC can be used.
The RNA that is loaded onto the APC can be provided to the APC as purified RNA, or as a fractionated preparation of a tumor or pathogen.
The RNA can include poly A.
sup.
+ RNA, which can be isolated by using conventional methods (e.
g.
, use of poly dT chromatography).
Both cytoplasmic and nuclear RNA are useful in the invention