Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21

Abstract

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 antigenspecific 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.

Highly Optimized DNA Vaccine Targeting Human Telomerase Reverse Transcriptase Stimulates Potent Antitumor Immunity

“…However, few studies have been performed to develop hTERT DNA vaccines. Previously, the DNA platform was studied in prime-boost strategies due to the low immunogenicity of hTERT DNA vaccines (47-49). Here, we developed a novel hTERT DNA vaccine using gene optimization strategies and demonstrated the vaccine delivered by EP induced strong cellular immune responses in both mice and NHP.…”

“…Previous studies have shown that xenogeneic melanoma-associated DNA vaccines can elicit effective anti-tumor immunity against murine melanoma (55, 56). Yamano et al found a human C-terminal TERT DNA vaccine induced effective anti-tumor immunity against TS/A murine breast cancer (47). Since the amino acid homology of NTE, RT and CTE regions between hTERT and murine TERT are 61.8%, 65.5% and 69.9%, respectively, the hTERT has regions of homology which may induce testable anti-tumor immunity against murine TERT-expressing tumor cells.…”

Xenogeneic immunization with human tyrosine hydroxylase DNA vaccines suppresses growth of established neuroblastoma

“…enhanced by using xenogeneic DNA, encoding for highly homologous proteins that are foreign to the species to be vaccinated (37,38).…”

Chemokines as Cancer Vaccine Adjuvants

“…As CCL21 is another potent inducer of T cell proliferation, Yamano et al injected CCL21 into mice at various time points before and after vaccination with TRP vaccine and showed CCL21 enhanced responses best when it was administered into the vaccine bed 24 hours prior to TRP DNA injection [44]. Another study tested CCL21 administration 24 hours before cTERT DNA vaccine [37]. Again, results showed significantly improved anti-TERT cell immunity in mice that received CCL21 chemokine compared to vaccine alone.…”