Table 1.
γc family cytokines in clinical trials about ACT
| Cytokines | NCT Number | Phase | Status | Tumor Type | Treatment of cytokines | ACT Type | The Role of Cytokines for T cells | Year |
|---|---|---|---|---|---|---|---|---|
| IL-2 | NCT03475134 | I | Active, not recruiting | Metastatic melanoma | High dose IL-2 after ACT | TIL | Promoting activation and proliferation | 2018 |
| NCT03171220 [139] | I/II | Unknown status | Advanced malignant solid tumor | IL-2 after ACT; NRTs combined with PD-1 inhibitor (SHR-1210) | Neoantigen reactive T cells (NRTs) | Promoting immune response after ACT | 2017 | |
| NCT01659151 | II | Active, not recruiting | Metastatic melanoma | High dose IL-2 after ACT | TIL | Promoting immune response after ACT | 2012 | |
| NCT02278887 [140] | III | Active, not recruiting | Metastatic Melanoma | High dose bolus IL-2 after infusion | TIL | Keeping the TIL active after ACT | 2014 | |
| NCT05505812 | Early phase I | Not yet recruiting | Advanced breast cancer | IL-2 after ACT | autologous TIL infusion (HS-IT101) | Promoting immune response after ACT | 2022 | |
| NCT05475847 | I | Recruiting | Cervical cancer | IL-2 after ACT | Autologous TIL(C-TIL052A) | Promoting immune response after ACT | 2022 | |
| NCT05361174 | I/II | Recruiting |
Unresectable melanoma, Metastatic melanoma, Stage III non-small cell lung cancer, Stage IV non-small cell lung cancer |
IL-2 after ACT | Genetically modified autologous TIL(IOV-4001) | Promoting immune response after ACT | 2022 | |
| NCT05194735 | I/II | Recruiting |
Gynecologic cancer, Colorectal cancer, Pancreatic cancer, NSCLC, CHOL, OV, Endometrial Cancer, Ovarian carcinoma Ovary neoplasm, Squamous cell lung cancer, Adenocarcinoma of lung, Adenosquamous cell lung cancer |
Aldesleukin (IL-2) with TCR-T treatment | Neoantigen specific TCR-T cell | Supporting growth and activation of TCR-T cells | 2022 | |
| NCT05141474 | Early phase I | Recruiting |
Epithelial Tumors, Malignant, Malignant Solid Tumor |
IL-2 infusion after ACT | Next-generation Neoantigen-selected TIL (NEXTGENTIL-ACT) | supporting the expansion of the infused cells. | 2021 | |
| IL-7 | NCT04833504 | Clinical follow-up study | Completed |
Diffuse large B-cell lymphoma, Mantle cell lymphoma, Transformed follicular lymphoma, Primary mediastinal large B-cell lymphoma |
CD19-CAR-T expressing IL-7 | CD19-CAR-T expressing IL-7 and CCL19(CD19-7 × 19 CAR-T treatment) | helping CAR T cells grow better and stay in the blood longer | 2021 |
| NCT04381741 | I | Recruiting | Diffuse large B-cell lymphoma | CD19 CAR-T expressing IL-7 | CD19-7 × 19 CAR-T plus PD1 monoclonal antibody | Promoting the survival of CAR-T cells in lymphoma tissue | 2020 | |
| NCT03932565 | I | Recruiting | Nectin4-positive advanced malignant solid tumor | expressing IL-7 of CAR-T cells | Nectin4/FAP-targeted fourth-generation CAR-T cells (expressing IL-7 and CCL19, or IL-12) | Promoting survival | 2019 | |
| NCT03929107 | II | Recruiting | B cell lymphoma | expressing IL-7 of CD19-CAR-T cells | Interleukin-7 and chemokine (C-C motif) ligand 19-expressing CD19-CAR-T cells | Promoting the survival | 2019 | |
| NCT03198546 [141] | II | Recruiting | Hepatocellular carcinoma | With IL-7/CCL19 secreting vector | GPC3/TGFβ-CART cells | Promoting the survival and expansion | 2017 | |
| C7R(IL-7R) | NCT04099797 | I | Recruiting |
Diffuse intrinsic pontine glioma, High grade glioma, Embryonal tumor, Ependymal tumor |
Expressing constitutively active IL-7 receptors | Autologous T lymphocytes expressing GD2-specific chimeric antigen and constitutively active IL-7 receptors (C7R-GD2.CART cells) | Giving the cells a constant supply of cytokine and helping them to survive for a longer period | 2019 |
| NCT03635632 | I | Recruiting | Relapsed or refractory neuroblastoma and other GD2 positive cancers (GAIL-N) | Expressing constitutively active IL-7 receptors | C7R-GD2.CART cells | Giving the cells a constant supply of cytokine and helping them to survive for a longer period | 2018 | |
| IL-15 | NCT05103631 | I | Recruiting | Liver Cell Carcinoma | Engineered CAR-T with IL-15 | Interleukin-15 armored glypican-3-specific chimeric antigen (GPC3-CAR) receptor expressing autologous T Cells (CATCH T cells) | helping CAR T cells grow better and stay in the blood longer | 2021 |
| NCT04377932 | I | Recruiting |
Pediatric solid tumors: Liver cancer, Rhabdomyosarcoma, Malignant rhabdoid tumor, Liposarcoma, Wilms tumor, Yolk sac tumor |
Engineered CAR-T with IL-15 | Interleukin-15 armored GPC3-CAR expressed in T cells (AGAR T cells) | helping CAR T cells grow better and stay in the blood longer | 2020 | |
| NCT03721068 | I | Recruiting |
Neuroblastoma Osteosarcoma |
Engineered CAR-T with IL-15 | iC9.GD2.CAR.IL-15 T-cells, GD2-CAR-T cells expressing IL–15, and the inducible caspase 9 safety switch (iC9) | allowing the CAR-T cells to survive and grow in vivo | 2018 | |
| NCT04844086 | I | Terminated | Advanced Lymphoid Malignancies | Engineered CAR-T with mbIL-15 | RPM CD19-mbIL15-CAR-T cells | allowing the CAR-T cells to survive and grow in vivo | 2021 | |
| IL-7 + IL-15 | NCT04186520 [142] | I/II | Recruiting | Relapsed refractory B cell malignancies | IL-7/IL-15 pre-treating CAR-T cells with flexible 8/12-day manufacturing and a fixed 12-day manufacturing process | CAR-20/19-T cells | Promoting CAR-T cells survival and expansion | 2019 |
| IL-2 vs. IL-7/IL-15 | NCT02992834 | IV | Unknown status | CD19+ B cell lymphoma | IL-2 vs. IL-7/IL-15 pre-treated CD19 TCR-T cells | Anti-CD19: TCRζ Chimeric Antigen Receptor-T Cells | Promoting expansion and survival | 2016 |
| NCT02652910 | I/II | Unknown status | B cell lymphoma | Manufacturing CD19.CAR-T cells through IL-7/IL-15 or IL-2-mediated expansion | anti-CD19 CAR-T cells |
IL-2: generating terminally differentiated effector cells; IL-7/IL-15: helping to selectively expand CAR-T cells with various memory phenotypes and improve persistency |
2016 | |
| IL-7 + IL-21 | NCT01087294 [143] | I | Active, not recruiting | Recurrent or persistent B-cell malignancies | Culturing CAR-T cells in media containing IL-21, IL-7, and TWS119 | Anti-CD19-CAR T cells | Helping differentiation into long-lived T cells and improving survival | 2010 |
| IL-2; IL-15 + IL-21; | NCT04729543 | I/II | Recruiting |
Melanoma; Melanoma, uveal; Head and neck cancer |
IL-15 and IL-21 cultivation; low dose of IL-2 administrations after ACT | autologous MC2 TCR T cells | Using IL-15 and IL-21 to generate young T cells; supporting T cells response by IL-2 | 2021 |
| IL-15 + IL-21 | NCT04093648 | I | Withdrawn |
Hepatocellular Carcinoma Hepatoblastoma |
Engineered CAR-T with IL-15 plus IL-21 | Interleukin-15 and − 21 armored glypican-3-specific chimeric antigen receptors expressed in T cells (CARE T cells) | helping CAR T cells grow better and stay in the blood longer | 2019 |
| NCT04715191 | I | Not yet recruiting |
Liver cancer, Rhabdomyosarcoma, Malignant rhabdoid tumor, Liposarcoma, Wilms tumor, Yolk sac tumor |
Engineered CAR-T with IL-15 plus IL-21 | Interleukin-15 and − 21 armored glypican-3-specific chimeric antigen receptors expressed in T cells (CARE T cells) | helping CAR T cells grow better and stay in the blood longer | 2021 |