Development and evaluation of the tumor vaccine TCL/CpG@GNP

doi:10.11958/20251525

Abstract

Abstract:

Objective To develop a tumor vaccine containing broad-spectrum neoantigen tumor cell lysate (TCL) and CpG adjuvant, and to effectively deliver it to lymph node dendritic cells. Methods A novel polymer, 9-fluorenylmethoxycarbonyl-polyethylene glycol-glycocholic acid (Fmoc-PEG-GCA), was employed to encapsulate the TCL and CpG through π-π stacking, resulting in high-density polyethylene glycol-modified glycocholic acid-decorated micelles TCL/CpG@GNP. The vaccine's drug loading, encapsulation efficiency, particle size, polydispersity index (PDI), zeta potential, morphology, stability, cellular safety, uptake capability, immune stimulation effects on bone marrow-derived dendritic cells (BMDCs) and in vivo anti-tumor efficacy were evaluated. Results The vaccine TCL and CpG demonstrated a drug loading capacity of 6.26% and the encapsulation rate was 37.59%. The drug loading capacity of CpG was 7.05%, and the encapsulation efficiency was 56.86%. The particle size measured (139.26±27.23) nm, with a PDI of 0.249±0.015, indicating favorable dispersion properties. The zeta potential was recorded at (-21.23±0.36) mV. The TCL/CpG@GNP vaccine demonstrated good stability, cell safety and uptake ability, and can promote the activation and maturation of BMDCs. In tumor-bearing mouse models, TCL/CpG@GNP inhibited tumor growth, increased the proportion of T lymphocytes in peripheral blood, and elevated IFN-γ levels in spleen. Conclusion The TCL/CpG@GNP tumor vaccine can effectively activate BMDCs and induce strong anti-tumor immune memory in a mouse lung cancer model.

Key words: cancer vaccines, tumor cell lysates, CpG adjuvant, immunotherapy

CLC Number:

R186.9，R730

Figures/Tables 9

Fig.1 Chemical structure characterization of TCL/CpG@GNP

Fig.2 TEM images of TCL/CpG@GNP (×200)

Fig.3 The stability of TCL/CpG@GNP in gastrointestinal tract

Fig.4 Cellular uptake ability of TCL/CpG@GNP (×200)

Fig.5 Immune-stimulatory effects of TCL/CpG@GNP

Tab.1 Comparison of IL-6 and IL-12 p70 levels in the culture supernatants of BMDCs between the three groups

组别	IL-6	IL-12 p70
PBS组	18.22±3.30	23.45±11.17
TCL+CpG+GNP组	21.55±3.22	34.51±7.60
TCL/CpG@GNP组	35.96±3.83^ab	380.72±25.70^ab
F	22.296^＊	440.623^＊＊

Fig.6 Tumor growth curves of the three groups of mice

Fig.7 The expression in mouse peripheral blood lymphocytes stimulated by TCL/CpG@GNP

Fig.8 The expression of mouse spleen lymphocytes stimulated by TCL/CpG@GNP

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