Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation

doi:10.5306/wjco.121101

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World Journal of Clinical Oncology

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World J Clin Oncol. Aug 24, 2026; 17(8): 121101
Published online Aug 24, 2026. doi: 10.5306/wjco.121101

Table 1 Summary of clinical trials evaluating interleukin-21 in cancer

Cancer type	Phase/status	Combination/intervention	Registration number
Malignant melanoma	Phase II	IL-21	NCT00514085; NCT00336986
Melanoma skin cancer	Phase II	Recombinant IL-21	NCT00601861
Metastatic or recurrent melanoma	Phase II	IL-21	NCT01152788
Ovarian cancer	Phase II	Recombinant IL-21; Caelyx	NCT00523380
Pancreatic cancer	Phase II	Recombinant human IL-21 expressing oncolytic vaccinia virus injection (hV01)	NCT07006077
Metastatic renal cell carcinoma	Phase I/II	Recombinant IL-21; sorafenib	NCT00389285
Renal cell carcinoma	Phase I/IIa	Recombinant human IL-21; sunitinib	NCT00617253
Advanced cancer	Phase I	Recombinant fusion protein of IL-21 and humanized anti-human serum albumin VHH antibody	NCT05296772
GPC3-positive solid tumors; liver cancer; ATRT and CNS rhabdoid tumors	Phase I	IL-15 and IL-21 armored GPC3-CAR T cells	NCT06198296; NCT04093648; NCT07513194
Melanoma	Phase I	Recombinant IL-21; ipilimumab	NCT01489059
Metastatic malignant melanoma and metastatic kidney cancer	Phase I	Recombinant IL-21	NCT00095108
Metastatic melanoma	Phase I	Recombinant IL-21	NN028-1614
Non-Hodgkin’s lymphoma	Phase I	Recombinant IL-21; rituxan	NCT00347971
Solid tumors	Phase I	IL-21; anti-PD-1	NCT01629758

IL-21: Interleukin-21; VHH: Variable domain of the llama heavy chain of heavy-chain antibody; ATRT: Atypical teratoid rhabdoid tumor; CNS: Central nervous system; CAR: Chimeric antigen receptor; PD-1: Programmed cell death protein 1.

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Citation: Wu JX, Jin YM, Shen WJ, Chen ZH, Zuo DB, Chen GP, Ji KK. Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation. World J Clin Oncol 2026; 17(8): 121101
URL: https://www.wjgnet.com/2218-4333/full/v17/i8/121101.htm
DOI: https://dx.doi.org/10.5306/wjco.121101

Wu JX, Jin YM, Shen WJ, Chen ZH, Zuo DB, Chen GP, Ji KK. Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation. World J Clin Oncol 2026; 17(8): 121101 [DOI: 10.5306/wjco.121101]

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