| First Author | Li Y | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 951 |
| PubMed ID | 33574265 | Mgi Jnum | J:304547 |
| Mgi Id | MGI:6515012 | Doi | 10.1038/s41467-021-21241-0 |
| Citation | Li Y, et al. (2021) Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy. Nat Commun 12(1):951 |
| abstractText | T cell rejuvenation by PD-1/PD-L1 blockade, despite emerging as a highly promising therapy for advanced cancers, is only beneficial for a minority of treated patients. There is evidence that a lack of efficient T cell activation may be responsible for the failure. Here, we demonstrate that IL-21 can be targeted to tumor-reactive T cells by fusion of IL-21 to anti-PD-1 antibody. To our surprise, the fusion protein PD-1Ab21 promotes the generation of memory stem T cells (TSCM) with enhanced cell proliferation. PD-1Ab21 treatment show potent antitumor effects in established tumor-bearing mice accompanied with an increased frequency of TSCM and robust expansion of tumor-specific CD8(+) T cells with a memory phenotype, and is superior to a combination of PD-1 blockade and IL-21 infusion. Therefore, we have developed a potential strategy to improve the therapeutic effects of immune checkpoint blockade by simultaneously targeting cytokines to tumor-reactive T cells. |
