Interleukin 2-Based Fusion Proteins for the Treatment of Cancer

Table 1

Select IL-2-based fusion constructs for cancer immunotherapy.

Fusion strategy		Description	Indication	Clinical status	Reference
Albumin	Albuleukin	Human serum albumin fused to IL-2	Solid tumors	Phase I	[37]
Fc	IL2-fc/IL2-Fc^3x	Murine IgG2c Fc region fused to IL-2. Triple mutant version contains R38D, K43E, and E61R mutations to attenuate Fc effector functions	B16F10 and CT26 tumor models	Preclinical	[47]
	CUE-101	IgG1 Fc with attenuated effector function, 2 peptide-HLA complexes, and 4 reduced affinity IL-2 domains	HPV+HNSCC	Phase I	[45]
	ProIL-2/sumIL2-fc	Human IgG1 Fc region fused to “superkine” IL-2 and a cleavable IL-2Rdomain	MC38 and B16 tumor models	Preclinical	[44]
Immunocytokine	L19-IL2	L19 antibody is specific for EDB splice isoform of fibronectin	Metastatic melanoma and renal cell carcinoma	Phase I/II	[97, 103, 104]
	F8-IL2	F8 antibody is specific for EDA splice isoform of fibronectin	Metastatic NSCLC and CT26 mouse models	Preclinical	[49, 55, 56, 105]
	F16-IL2	F16 antibody specific for A1 domain of tenascin C	Glioblastoma, breast cancer	Preclinical, phase I/II	[58, 60, 98]
	hu14.18-IL2	hu14.18 antibody is specific for disialoganglioside (GD2)	Neuroblastoma, metastatic melanoma	Phase I/II, phase II	[106–108]
	huKS-IL2 (EMD 273066, tucotuzumab celmoleukin)	huKS antibody is specific for epithelial cell adhesion molecule (EpCAM)	EpCAM+advanced solid tumors	Phase I	[99]
	NHS-IL2 LT (EMD 521873, selectikine)	NHS antibody is specific for necrotic DNA fused to IL-2 containing a D20T mutation	Advanced solid tumors, metastatic NSCLC	Phase I	[100, 109]
	B3-IL2	Heavy chain only antibody fragment specific for PD-L1	Pan02 and KPC tumor models	Preclinical	[63]
	2aG4-IL2	2aG4 antibody is specific for exposed phosphatidylserine on cell surface	4T1 mouse model	Preclinical	[69]
Immunotoxin	DAB389-IL2 (Ontak)	DT with a 97 amino acid in-frame deletion fused to IL-2 at the DT receptor binding site	CTCL, CLL, non-Hodgkin’s lymphoma, NSCLC	FDA approved for CTCL	[75]
PEG	Bempegaldesleukin (NKTR-214)	IL-2 with approximately 6 cleavage PEG chains positioned near the CD25 binding domain	Advanced or metastatic solid tumors	Phase I/II	[86, 87]
	THOR-707 (SAR444245)	IL-2 with one noncleavable PEG chain attached to a novel amino acid insertion	Solid tumors	Preclinical, phase I/II	[46, 89], NCT04009681