bifikafusp alfa   Click here for help

GtoPdb Ligand ID: 9756

Synonyms: Darleukin | L19-IL2 | L19IL2
Immunopharmacology Ligand
Compound class: Antibody
Comment: Bifikafusp alfa (Darleukin) is a fusion protein of pro-inflammatory IL-2 and an L19 human mAb fragment (scFv domain) that binds the tumour microenvironment expressed fibronectin extradomain B (EDB) [1]. Structurally it is a diabody with two IL-2 units per molecule. Incorporation of the L19 binding fragment targets the drug to the tumour, improving selective site accumulation and tumour killing and at the same time reducing the effective dose required to achieve a meaningful response, and reducing the otherwise dose-limiting toxicities associated with high-dose IL-2 administration that would be required to produce the same killing effect. Darleukin is one of a growing number of so-called 'immunocytokines' entering clinical development.
1. Carnemolla B, Borsi L, Balza E, Castellani P, Meazza R, Berndt A, Ferrini S, Kosmehl H, Neri D, Zardi L. (2002)
Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix.
Blood, 99 (5): 1659-65. [PMID:11861281]
2. Danielli R, Patuzzo R, Di Giacomo AM, Gallino G, Maurichi A, Di Florio A, Cutaia O, Lazzeri A, Fazio C, Miracco C et al.. (2015)
Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study.
Cancer Immunol Immunother, 64 (8): 999-1009. [PMID:25971540]
3. List T, Neri D. (2013)
Immunocytokines: a review of molecules in clinical development for cancer therapy.
Clin Pharmacol, 5: 29-45. [PMID:23990735]
4. Viti F, Tarli L, Giovannoni L, Zardi L, Neri D. (1999)
Increased binding affinity and valence of recombinant antibody fragments lead to improved targeting of tumoral angiogenesis.
Cancer Res, 59 (2): 347-52. [PMID:9927045]