Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy

Anti-CTLA-4 antibodies have been widely utilized in cancer therapy owing to their capacity to activate tumor immunity by reversing intratumoral immune suppression. However, whether these antibodies can exert an anti-tumor vaccinal effect—with considerable clinical implications for preventing tumor recurrence—remains largely unexplored. In the present study, anti-CTLA-4 antibody treatment induced complete regression of established Hepa1-6 tumors in a subset of mice. More notably, cured mice developed a robust anti-tumor vaccinal effect persisting over 50 weeks. Critically, anti-CTLA-4 pretreatment inhibited tumor growth, drove regression and conferred potent vaccinal effect upon rechallenge with the same tumor cells. Furthermore, tumor-specific immune mice were protected against distant metastasis. Mechanistically, complete regression correlated with increased effector memory T cell proportions. Depletion experiments confirmed that T and NK cell depletion fully abrogated the antibody-induced vaccinal effect. Most intriguingly, adoptive transfer of PBMCs from immune mice into naive recipients via tail vein injection conferred Hepa1-6-specific immunity. Collectively, our findings establish the vaccinal potential of anti-CTLA-4 antibody and provide a promising strategy to prevent tumor recurrence.