Dendritic cells infected with recombinant adenoviral vector encoding mouse fibroblast activation protein‐α and human livin α exert an antitumor effect against Lewis lung carcinoma in mice

Autor: Zaiting Ye, Jiongwei Pan, Zhangyong Yin, Shuanghu Wang, Yuling Li, Xiaoping Cai, Hao Zheng, Zhuo Cao
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Immunity, Inflammation and Disease, Vol 11, Iss 9, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2050-4527
DOI: 10.1002/iid3.1011
Popis: Abstract Background Fibroblast activation protein‐α (FAP) and livin α are considered as cancer‐associated fibroblasts (CAFs) and tumor‐specific targets, respectively, for immunogenic tumor vaccines. This study is designed to decipher the antitumor effect of double‐gene modified dendritic cells (DCs) on Lewis lung carcinoma (LLC). Methods By encoding mouse FAP cDNA and human livin α (i.e., hlivin α) cDNA into recombinant adenoviral vector (rAd), rAd‐FAP, rAd‐hlivin α, and rAd‐FAP/hlivin α were constructed, which were then transduced into mouse DCs. LLC‐bearinig mice were immunized with the infected DCs (5 × 105 cells/mouse), followed by calculation of tumor volume and survival rate. The identification of CAFs from mouse LLC as well as the determination on expressions of FAP and livin α, was accomplished by western blot. Cytotoxic T lymphocyte assay was harnessed to assess the effect of the infected DCs on inducing splenic lymphocytes to lyse CAFs. Results DCs were successfully transduced with rAd‐FAP/hlivin α in vitro. FAP was highly expressed in CAFs. CAFs were positive for α‐SMA and negative for CD45 and CD31. Livin α level was upregulated in mouse LLC. Immunization with rAd‐FAP/hlivin α‐transduced DCs suppressed LLC volume and improved the survival of tumor‐bearing mice. Immunization with rAd‐FAP/hlivin α‐transduced DCs enhanced the cytotoxic effect of splenic lymphocytes on LLC tumor‐derived CAFs. Conclusion Injection with rAd‐FAP/hlivin α‐transduced DCs promotes immune‐enhanced tumor microenvironment by decreasing CAFs and suppresses tumor growth in LLC mouse models.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje