Table 5.
The main preclinical studies of cytokine therapy.
| Target | Effects | Tumor type | Species | Combined therapy | Ref |
| IL-2 |
IL-2/NARA1 complex
1. IL-2 and NARA1 (NARA1, high-affinity CD25 mimic, avoiding vascular leak syndrome caused by Tregs activation); 2. In vivo; 3. Inhibited tumor growth; 4. Expanded tumor-specific CD8+ T cells with better effector function; |
Melanoma (B16-F10) |
M | / | (80) |
|
SIL2-EMSCs
1. Engineered MSCs for targeting IL-2 to activate CD8 T cells in TME; 2. In vivo; 3. Expanded Tpex; 4. Promoted the production of IFN-γ in terminal exhausted T cells; |
Melanoma (B16); Colon cancer (MC38, CT26) |
M | PD1/PDL1 blockade |
(81) | |
|
PD-1-cis-targeted IL-2Rβγ agonists
1. Bound to PD-1 and IL-2Rβγ; 2. In vivo; 3. Suppressed tumor growth; 4. Expanded CD8+ TILs with better effector function; 5. Decreased the expression of exhaustion-related genes such as Havcr2, Tigit and Tox in CD8+ TILs; 6. Increased expression of genes involved in productive and protective immune memory in CD8+ TILs; |
Pancreatic tumor (Panc02-H7) |
M | / | (21) | |
| IL-10 |
IL-10/Fc
1. In vivo; 2. Expanded terminally exhausted subsets (self-renewal); 3. Improved cytotoxicity of terminally exhausted subsets; |
Melanoma (B16-F10); Colon Cancer (CT26) |
M | PD1/PDL1 blockade |
(72) |
| IFN |
Knockdown irnar1 in T cells
1. Evaluated the anti-tumor effects of knockdown of irnar1; 2. Inhibited the growth; 3. Increased the number of CD8+ TILs, characterized by the decreased expression of TIM3, CTLA-4, LAG3 and TOX and the enhanced expression of TCF1; |
Liver cancer (Delivering oncogenes NRAS and AKT into hepatocytes) |
M | PD1/PDL1 blockade |
(82) |
|
IRF2-deficient CD8+ T cells (CD8-irf2 cKO mice)
1. ACT (transfer of IRF2-deficient CD8+ T cells into tumor model); 2. Slowed down tumor growth; 3. Low expression of inhibitory receptors and the enhanced production of Granzyme B, perforin and IFN-γ; 4. No expression of TOX; |
Colon Cancer (MC38) | M | PD1/PDL1 blockade |
(76) |
The table summarized the main preclinical studies of cytokine therapy. Tumor: tumor cell lines in mouse model or method. M, mouse; Ref, references; ACT, adoptive cell transfer therapy.