Table 1.
Approaches, discussed in the review, to promote thymic function, their targets and their evaluation in clinical trials.
| Therapeutic Approach | Targets cells | Clinical Translation | References | |
|---|---|---|---|---|
| Trial | Setting | |||
| Cytokines | ||||
| IL-7 | HSPCs, thymocytes, mature T cells |
NCT01190111 NCT01241643 NCT00839436 NCT00684008 NCT00477321 NCT04332653 |
HIV HIV ICL HCT HIV Advanced solid tumors (anti-PD1) |
(66) (67) (68) (69) (70) (70) (71) (72, 73) |
| IL-12 | Thymocytes | Pre-clinical | (74) (75) |
|
| IL-21 | HSPCs, thymocytes | Pre-clinical | (76) (77) (78) |
|
| IL-22 | TECs | Pre-clinical | (79) (80) |
|
| RANKL | TECs | Pre-clinical | (81) (82) (83) |
|
| Growth Factors | ||||
| KGF | TECs |
NCT00593554 NCT02356159 NCT03042585 NCT01233921 NCT01712945 |
HCT HCT HCT HCT MS |
(84) (85) (86) (87) (88) (69) (89) |
| IGF-1 | TECs | Pre-clinical | (90) | |
| BMP4 | TECs | Pre-clinical | (91) | |
| Hormones | ||||
| Thymosin-α1 | Thymocytes |
NCT00580450 NCT00911443* |
HCT Melanoma* |
(92, 93) (94) (92) (95) |
| GH | TECs, thymocytes |
NCT00287677 NCT00071240 NCT00050921 NCT00119769 NCT04375657 |
HIV HIV HIV HIV Immunosenescence |
(96) (97) (98) (99) (100) (101) |
| Sex steroid ablation | TECs, HSPCs, thymocytes |
NCT01746849 NCT01338987 NCT03650894 |
HCT HCT Breast cancer (anti-PD1+ anti-CTLA4) |
(102) (63) (103) (104) (105) (106) (105) (107) (108, 109) |
| Artificial Tissue | ||||
| Artificial Thymus | TECs, thymocytes | Pre-clinical | (110) (111) (112, 113) (114) |
|
In bold, clinical studies on CBI in combination with immune boosting strategy. (GH, growth hormone; HSPCs, hematopoietic stem and progenitor cells; KGF, keratinocyte growth factor; IL, interleukin; RANKL, receptor activator of nuclear factor-κB ligand; TECs, thymic epithelial cells; IGF1, insuline-like growth factor 1; HCT, hematopoietic cell transplantation; MS, multiple sclerosis; ICL, Idiopathic CD4+ lymphocytopenia; HIV, Human Immunodeficiency Virus).
*Clinical trial on the efficacy of thymosin-α1 in combination with dacarbazine in melanoma patients. Patients were subsequently treated with anti-CTLA4 in a separate study.