Induction of anti-tumor immunity with epidermal cells pulsed with tumor-derived RNA or intradermal administration of RNA

The skin is well-suited to serve as a substrate for vaccination strategies. In this regard, epidermal cells exposed to granulocyte-macrophage colony-s timulating factor can, upon subcutaneous injection into naive mice, present a soluble extract of tumor as a source of tumor-associated antigens for th e induction of in vivo anti-tumor immunity. Use of RNA for immunization has a potential advantage over this technique. Because RNA can be amplified, o nly a small amount of tumor is needed for antigen preparation and, as with a soluble extract, it is not necessary to know the molecular nature of the antigen(s) relevant to immunity. To test the hypothesis that RNA-pulsed epi dermal cells can induce anti-tumor immunity, total cellular RNA was isolate d from the S1509a spindle cell tumor and used to pulse CAF(1) epidermal cel ls enriched for Langerhans cell content and pre-exposed to granulocyte-macr ophage colony-stimulating factor. These cells were then injected subcutaneo usly into naive CAF(1) mice three times at weekly intervals followed by cha llenge with living S1509a cells. Tumor growth was significantly less than i n control animals immunized in an identical fashion but with irrelevant RNA . Digestion of S1509a RNA with RNase prior to pulsing of epidermal cells pr evented the development of immunity. In separate experiments, intradermal i njection of S1509a RNA into naive mice three times at weekly intervals also induced immunity to challenge with the tumor. Digestion of S1509a RNA with RNase also prevented development of immunity in this system. Effective ant i-tumor immunity can be induced in mice utilizing RNA-pulsed epidermal cell s for in vivo immunization or by injecting RNA intradermally into naive mic e.