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.
Hsieh
Chia-Jung
CJ
Department of Pathology, The Johns Hopkins University School of Medicine, Richard Ross Research Building, Baltimore, MD 21205, USA.
Kim
Tae Woo
TW
Hung
Chien-Fu
CF
Juang
Jeremy
J
Moniz
Michelle
M
Boyd
David A K
DA
He
Liangmei
L
Chen
Pei-Jer
PJ
Chen
Chien-Hung
CH
Wu
T-C
TC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D037282:Calreticulin / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D002461:Cell Line, Transformed; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D037282:Calreticulin; D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma