Table 2 Recently reported γc family cytokines or responding receptor engineered for transferred T cells stemness
From: New insights into the stemness of adoptively transferred T cells by γc family cytokines
Publication | Year | γc family cytokines | Engineered version | Discovery | |
|---|---|---|---|---|---|
Mo F et al. [76] | 2021 | IL-2 | H9T, an engineered IL-2 partial agonist. | The H9T sustained the stemness of TCR-T and CAR-T cells through altered STAT5 signaling, mediating robust antitumor activity in vivo. | |
Aspuria PJ.et al. [79] | 2021 | IL-2 | Orthogonal IL-2/IL-2Rβ pair, an orthogonal human IL-2 (STK-009) selectively pairs with an orthogonal human IL-2Rβ (hoRb) expressed on CAR T cells. | STK-009 expanded hoRb-expressing CAR T cells and maintained the presence of TSCM. | |
Kalbasi A et al. [10] | 2022 | IL-2 and IL-9 receptors | Orthogonal IL-2-O9R pair, IL-2Rβ-ECD-IL-9R-ICD (o9R), the chimeric receptor that orthogonal IL-2 receptor extracellular domain was fused with the intercellular domain of IL-9. | Co-culture of o9R-transduced pmel TCR-T cells with specific oIL-2 upregulated T cell stemness genes resulted in fantastic tumor eradication for ACT. | |
Hurton LV et al. [116] | 2016 | IL-15 | mbIL-15, the mbIL15-CAR T cells co-expressing CAR with a membrane-bound chimeric IL-15 to incorporate the costimulatory properties of IL-15. | The mbIL-15 instructed CAR-T cells to possess a memory stem cell-like transcriptional profile and developed stemness attributes. | |
Guo J. et al. [123] | 2021 | IL-15 | pro-IL-15, a next-generation IL-15 with the extracellular domain of IL-15Rβ fused to the N-terminus of super-IL-15-Fc (IL-15 fused with the IL-15Rα sushi domain) through a tumor-enriched Matrix Metalloproteinase (MMP) cleavable peptide linker to block its activity. | The pro-IL-15 specifically promoted stem-like CD8(+) T cells including infused T cells inside the TME making it possible to expand and persist of infused TSCM in TME. | |
Li Y. et al. [130] | 2021 | IL-21 | The fusion protein PD-1Ab21 by fusion of IL-21 to anti-PD-1antibody can be targeted to tumor-reactive T cells. | PD-1Ab21 promoted TSCM generation and showed impressive antitumor effects. | |