Enhancement of Vaccinia Vaccine Potency by Linkage of Tumor Antigen Gene to Gene Encoding Calreticulin

Vaccinia vaccines have become important vectors for antigen- specific immunotherapy. Calreticulin has been shown to enhance MHC class I presentation of linked peptide/protein and may be useful for antigen- specific cancer treatment. An innovative vaccine administering antigen linked to calreticulin via a vaccinia vector may generate a potent antigen -specific antitumor response. We tested the efficacy of linking calreticulin (CRT) to model antigen human papilloma virus type 16 (HPV-16) E7 in the context of a vaccinia vaccine (Vac-CRT/E7). Intraperitoneal vaccination of C57BL/6 mice with Vac-CRT/E7 led to a dramatic increase in E7-specific IFN-gamma-secreting CD8(+) T cells and a potent antitumor effect against E7-expressing tumors compared to immunization with Vac-E7 or Vac-CRT. When compared to other chimeric vaccinia vaccines employing various intracellular targeting strategies previously developed in our lab , Vac-CRT/E7 elicited the highest number of E7-specific CD8(+) T cells. Thus, vaccination with vaccinia expressing CRT linked to a tumor antigen may represent an advantageous strategy for cancer immunotherapy. (C) 2004 Elsevier Ltd. All rights reserved