Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct;25(10):2972-2982.
doi: 10.1007/s12094-023-03161-1. Epub 2023 Apr 20.

DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors

Miaomiao Zhang #  1 , Yuanyuan Wang #  1 , Xinzu Chen  1 , Fan Zhang  1 , Jiannan Chen  1 , Hongqiao Zhu  1 , Jun Li  2 , Zhengliang Chen  2 , Aying Wang  3 , Yao Xiao  4 , Zilu Chen  4 , Yunfei Dong  1 , Xuechen Yin  1 , Feng Ji  1 , Jie Liu  1 , Junqing Liang  5 , Feiyan Pan  1 , Zhigang Guo  1 , Lingfeng He  6
Affiliations

DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors

Miaomiao Zhang et al. Clin Transl Oncol. 2023 Oct.

Abstract

Objective: Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors.

Methods: To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR.

Results: The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo.

Conclusion: In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.

Keywords: DC vaccine; Infiltration; MSLN CAR-T; Persistence; Solid tumor.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhang C, Liu J, Zhong JF, et al. Engineering CAR-T cells. Biomak Res. 2017. https://doi.org/10.1186/s40364-017-0102-y . - DOI
    1. Cao J, Wang G, Cheng H, et al. Potent anti-leukemia activities of humanized CD19-targeted Chimeric antigen receptor T (CAR-T) cells in patients with relapsed/refractory acute lymphoblastic leukemia [J]. Am J Hematol. 2018;93(7):851–8. - DOI - PubMed
    1. Wei G, Ding L, Wang J, et al. Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017. https://doi.org/10.1186/s40164-017-0070-9 . - DOI - PubMed - PMC
    1. Han D, Xu Z, Zhuang Y, et al. Current progress in CAR-T cell therapy for hematological malignancies [J]. J Cancer. 2021;12(2):326–34. - DOI - PubMed - PMC
    1. Newick K, O’Brien S, Moon E, et al. CAR T Cell Therapy for Solid Tumors [M]//CASKEY C T. Annu Rev Med. 2017;68:139–52. - DOI - PubMed

LinkOut - more resources