Co‐immunization with L‐Myc enhances CD8 + or CD103 + DCs mediated tumor‐specific multi‐functional CD8 + T cell responses

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle‐mediated DNA vaccine containing an activated factor L‐Myc and a tumor‐specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS‐pL‐Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS‐pL‐Myc/pCAIX co‐immunization group. The increased proportion and mature of CD11c+ DCs, CD8+CD11c+ DCs and CD103+CD11c+ DCs were observed in the splenocytes from CS‐pL‐Myc/pCAIX co‐immunized mice. Furthermore, the enhanced antigen‐specific CD8+ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi‐functional CD8+ T cell induction were detected in CS‐pL‐Myc/pCAIX co‐immunization group compared with CS‐pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8+ T cells or CD8+CD11c+ DCs and the loss of anti‐tumor efficacy induced by CS‐pL‐Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8+ DCs and CD103+ DCs mediated CD8+ T cells responses. Likewise, CS‐pL‐Myc/pCAIX co‐immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi‐functional CD8+ T cell responses. Therefore, these results indicated that CS‐pL‐Myc/pCAIX vaccine could effectively induce CD8+ DCs and CD103+ DCs mediated tumor‐specific multi‐functional CD8+ T cell responses and exert the anti‐tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.
CS‐p‐L‐Myc/pCAIX vaccine activated the CD8+CD11c+ DCs and CD103+CD11c+ DCs, and activated CAIX‐specific CD8+ T cell proliferation, CTL responses, and multi‐functional CD8+ T cells (expressing TNF‐α, IL‐2, and IFN‐γ) in mouse tumor models. Moreover, the CD8+ T cell depletion resulted in the reduction of CD8+CD11c+ DCs and the loss of anti‐tumor activity of vaccine, suggesting that this therapeutic efficacy was required for CD8+CD11c+ DCs‐mediated multi‐functional CD8+ T cell responses. Therefore, this vaccine strategy may be a potential approach for primary solid or metastasis tumor therapy.