Table 2.
Preclinical studies exploring soluble factors and cellular therapies to enhance T-cell function after HCT.
| Factor/method | Target | Selected recent references |
|---|---|---|
| Soluble factors | ||
| Interleukin-7* | Haematopoietic progenitor cells, thymocytes, peripheral T lymphocytes | (24, 158–161) |
| Interleukin-12 | Thymocytes | (162, 163) |
| Interleukin-15 | NK/NKT cells, CD8+ T cells | (164, 165) |
| Interleukin-21 | Thymocytes, haematopoietic progenitor cells | (166) |
| Interleukin-22 | Thymic epithelial cells | (167, 168) |
| FMS-like tyrosine kinase 3 (FLT3) ligand | Hematopoietic progenitor cells | (169–171) |
| Insulin-like growth factor 1 | Thymic epithelial cells, myeloid cells | (172, 173) |
| Keratinocyte growth factor* | Thymic epithelial cells | (116, 174–177) |
| Receptor activator of NF-κB ligand (RANKL) | Thymic epithelial cells | (178), Montero-(179) |
| Stem cell factor | Thymocytes | (180) |
| Thymosin alpha 1* | Thymic epithelial cells, thymocytes | (181), (182) |
| Sex hormone ablation* | Thymic epithelial cells, thymocytes, haematopoietic progenitor cells | (183–186) |
| Growth hormone* | Thymic epithelial cells, thymocytes | (187) |
| Cellular therapies | ||
| Precursor T cells (ex vivo generated by Notch-1 ligand delta-like-1 or Notch ligand delta-like-4 containing cocktails from HSC)* | Thymic epithelial cells, thymocytes | (188, 189) |
| Thymic epithelial cells (ex vivo generated by Foxn1 containing cocktail from fibroblasts, embryonic stem cells or iPSCs) | Thymic epithelial cells, thymocytes | (190–192) |
| Mesenchymal stromal cells (ex vivo expanded)* | Haematopoietic progenitor cells, thymic epithelial cells, T cells | (193, 194) |
| Anti-Viral Central Memory CD8 Veto Cells* | Donor-specific host T cells, host leukemic cells, virally infected cells | (195, 196) |
| Regulatory T cells | Alloreactive conventional donor T cells | (197, 198) |
| Endothelial cells (ex vivo expanded) | Thymic epithelial cells | (199) |
| Injectable thymus organoids | Common lymphoid precursors, peripheral T cells | (200, 201) |
Table adapted from Velardi et al. (6). *Principles already investigated or being investigated in ongoing clinical studies. HSC, haemopoietic stem cell; iPSC, induced pluripotent stem cells.