Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21.
Human telomerase reverse transcriptase (TERT) has been considered a potential tumor-associated antigen for active-specific immunotherapy. However, effective specific tumor antigen-specific immunity has been difficult to induce consistently by various TERT vaccine formulations. New adjuvant strategies have been employed, such as utilizing chemokines to attract T cells and antigen-presenting cells. Chemokine adjuvant strategies may enhance tumor antigen-specific immunity induced by vaccines. Therefore, we utilized chemokine ligand 21 (CCL21) as an adjuvant with a xenogeneic TERT DNA vaccine to induce tumor antigen-specific immunity against TERT-expressing breast cancer. The TERT DNA vaccine consisted of a plasmid containing the COOH terminal end of the TERT (cTERT) gene, encapsulated in multilayered liposomes with hemagglutinating virus of Japan coating. We demonstrated that CCL21 treatment before cTERT DNA vaccine, given intramuscularly, induced significantly higher anti-TERT specific cell-mediated immunity compared to cTERT DNA vaccine alone. Effective tumor antigen-specific immunity was shown both in prophylactic and therapeutic regimens against TS/A murine breast cancer. The study demonstrated that CCL21 administration before cTERT DNA vaccination significantly augmented tumor antigen-specific immunity against breast cancer.
Yamano
T
T
Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA 90404, USA.
Kaneda
Y
Y
Hiramatsu
S H
SH
Huang
S
S
Tran
A N
AN
Giuliano
A E
AE
Hoon
D S B
DS
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000627:therapeutic use
D000951:Antigens, Neoplasm; C515478:CCL21 protein, human; D019496:Cancer Vaccines; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D019444:Vaccines, DNA; C509186:TERT protein, human; D019098:Telomerase