Anlotinib and anti-PD-1 mAbs perfected CIK cell therapy for lung adenocarcinoma in preclinical trials

Murine cytokine-induced killer (CIK) cells are heterologous cells that kill various allogeneic and isogenic tumors and have functional and phenotypic characteristics of natural killer cells and T lymphocytes. However, the effect of CIK cells alone on solid tumor therapy is only limited. To enhance the therapeutic effect, it is vital to discover a mix of several therapy approaches. Immune cell function is inhibited by abnormal tumor vessels and the tumor microenvironment, which block lymphocyte entry into tumor tissue. To increase the effectiveness of CIK cells' antitumor activity, antivascular therapy and CIK cell therapy can be combined. Furthermore, anlotinib is a tiny drug with multitarget tyrosine kinase inhibitors that can block cell migration, delay angiogenesis, and decrease blood vessel density. Compared with other antiangiogenesis drugs, anlotinib stands out due to the wider target of action and lower effective dose. In this work, anlotinib and murine CIK cells were coupled to boost CD3+ T cell infiltration, CD3+CD4+ T cell infiltration, and expression of granzyme B and interferon γ from CD3+CD8+ T cells, which increased the antitumor activity. Through the generation of cytotoxic cytokines by T lymphocytes, the therapeutic group using anti-PD-1 monoclonal antibodies in conjunction with anlotinib and CIK cells was more successful than the group receiving dual therapy. The preclinical study contributes to exploring the therapeutic alternatives for patients with lung adenocarcinoma, thus prolonging their lives.