Chemokine-enhanced DNA vaccination in cancer immunotherapy

Abstract

We have demonstrated that priming of intratumoral and intradermal vaccination sites with chemokines enhances cytotoxic immune response against established neoplasms. Additional insights into the molecular mechanisms that underlie these findings and the optimization of such an approach may lead to the development of cost-effective and generic immunotherapeutic regimens against cancer.

Keywords: DNA vaccine; chemokines; intradermal vaccination; intratumoral vaccination; leukocyte recruitment; therapeutic vaccine.

Figure 1. Intratumoral and intradermal chemokine-enhanced DNA-based anticancer vaccination. (1) Priming of intratumoral (A) and intradermal (B) vaccination sites with chemokines. (2) Chemokine-mediated recruitment of T cells alone (A) or accompanied by immature antigen-presenting cells (APCs) (B). (3) Administration of DNA-based vaccines into chemokine-primed tissues, leading to enforced antigen expression by immature APCs, APC maturation, extranodal antigen presentation via MHC class I mechanism , and T-cell activation. (4) Immediate recognition of target (cancer) cells by activated antigen-specific cytotoxic T lymphocytes (CTLs) and CTL expansion (A), or emigration of activated CTLs from the skin to antigen-expressing neoplastic lesions and relocation of vaccinated APCs to draining lymph nodes (LNs) and intranodal T-cell activation (B). (5) Killing of antigen-expressing target cells by activated CTLs.