Kadam Pournima, Singh Ram P, Davoodi Michael, Lee Jay M, John Maie St, Sharma Sherven
Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Vaccines (Basel). 2020 Nov 5;8(4):655. doi: 10.3390/vaccines8040655.
Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines.
Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine.
Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies.
PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.
下调T细胞逃逸以实现有效免疫的免疫检查点阻断疗法重新激发了人们对治疗性癌症疫苗的兴趣。
利用小鼠肺癌模型，我们测定了：肿瘤负荷、肿瘤浸润淋巴细胞（TIL）细胞溶解作用、免疫组织化学、流式细胞术、RNA测序、CD4 T细胞、CD8 T细胞、CXCL9趋化因子和CXCL10趋化因子中和作用，以评估程序性细胞死亡蛋白1（PD-1）阻断与趋化因子（C-C基序）配体21-树突状细胞肿瘤抗原（CCL21-DC肿瘤抗原）疫苗联合使用的疗效。
抗PD1与CCL21-DC肿瘤抗原疫苗联合使用可根除75%已形成12天的肿瘤（直径150毫米），在联合治疗前先给予CCL21-DC肿瘤抗原疫苗可将根除率提高到90%。联合治疗的效果被CD4、CD8、CXCL9和CXCL10中和抗体阻断。
PD-1阻断疗法加CCL21-DC肿瘤抗原疫苗可能对肺癌患者有益。
