A Tumor-Targeting C-Terminal Fragment of Recombinant Human Calcineurin B Retains Immunostimulatory and Antitumor Activities

Recombinant human calcineurin B subunit (rhCNB) has been reported to exhibit potent antitumor activity through activation of innate and adaptive immune responses. However, the functional domain responsible for its tumor-targeting and immunostimulatory properties remains unclear. In this study, we constructed a truncated C-terminal fragment of rhCNB (designated DC, amino acids 85–169) to investigate its biological functions. The recombinant DC protein was successfully expressed and purified from E. coli . Functional characterization demonstrated that DC retained the key biological activities of rhCNB. Confocal imaging revealed that DC rapidly entered tumor cells, similar to full-length rhCNB. In vivo imaging further showed that DC effectively accumulated in tumor tissues and exhibited enhanced tumor retention. In addition, DC promoted the maturation of bone marrow-derived dendritic cells and significantly increased the secretion of proinflammatory cytokines and chemokines. Moreover, DC synergistically enhanced the cytotoxic effects of paclitaxel on multiple tumor cell lines. Importantly, administration of DC in H22 tumor-bearing mice significantly inhibited tumor growth, achieving a tumor inhibition rate comparable to that of rhCNB. Collectively, these findings identify the C-terminal region of rhCNB as a critical functional domain responsible for tumor targeting and antitumor activity. The DC fragment represents a promising candidate for the development of tumor-targeting therapeutics and peptide-based drug delivery systems.