Abstract
The induction of long-lived effector CD8+ T cells is key to the development of efficient cancer vaccines. In this study, we demonstrated that a Toll-like receptor 2 (TLR2) agonist-fused antigen increased antigen presentation via TLR2 signaling and induced effector memory-like CD8+ T cells against cancer after immunization. The N-terminus of ovalbumin (OVA) was biologically fused with a bacterial lipid moiety TLR2 agonist to produce a recombinant lipidated ovalbumin (rlipo-OVA). We demonstrated that rlipo-OVA activated bone marrow-derived dendritic cells (BM-DCs) maturation and increased antigen presentation by major histocompatibility complex (MHC) class I via TLR2. After immunization, rlipo-OVA skewed the immune response towards T helper (Th) 1 and induced OVA-specific cytotoxic T lymphocyte (CTL) responses. Moreover, immunization with rlipo-OVA induced higher numbers of effector memory (CD44+CD62L−) CD8+ T cells compared with recombinant ovalbumin (rOVA) alone or rOVA mixed with the TLR2 agonist Pam3CSK4. Accordingly, the CD27+CD43+ effector memory CD8+ T cells expressed high levels of the long-lived CD127 marker. The administration of rlipo-OVA could inhibit tumor growth, but the anti-tumor effects were lost after the depletion of CD8 or CD127 cells in vivo. These findings suggested that the TLR2 agonist-fused antigen induced long-lived memory CD8+ T cells for efficient cancer therapy.
Highlights
IntroductionThe induction of antigen-specific CD8+ T cells with cytolytic activity capable of killing cancer cells is critical [1]
Cancer vaccines are designed to prevent cancer formation or eliminate cancer cells
The recombinant antigens were engineered to contain a hexahistidine tag (HisTag) at their C-terminus and expressed in an Escherichia coli system under the control of the T7 promoter (Figure 1A). recombinant ovalbumin (rOVA) was purified from the lysates using immobilized metal affinity chromatography (IMAC) and polished using anion-exchange chromatography (Figure 1B, lanes 1–5)
Summary
The induction of antigen-specific CD8+ T cells with cytolytic activity capable of killing cancer cells is critical [1]. The quantity and quality of antigen-specific cytotoxic T lymphocytes (CTLs) have been proposed to play an important role in their therapeutic effects [2]. The primed antigen-specific CD8+ T cells undergo clonal expansion, resulting in the contraction of effector cells and the establishment of memory cells [3]. The induction of long-lived memory cells is considered an important factor in efficient antitumor immunity. A cancer vaccine should skew the T cell response to T helper (Th) 1 responses that facilitate the production of potent CTLs and memory CD8+ T cells [1, 4, 5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
