bintrafusp alfa

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Ligands
bintrafusp alfa

GtoPdb Ligand ID: 11376

Synonyms: M7824 | MSB0011359C

Comment: Bintrafusp alfa (M7824) is an investigational bifunctional fusion protein that combines two TGFβ 'trap' domains (derived from the extracellular domain of TGFBR2) that are linked to each of the C-terminal domain of the heavy chains of an anti-PD-L1 IgG1 monoclonal (mAb) [1,3]. The antibody component is similar to the anti-PD-L1 mAb avelumab and similarly, bintrafusp alfa was developed as a cancer immunotherapeutic [5]. Based on evidence that both the TGFβ pathway and the PD-PD-L1/PD-1 immune checkpoint are associated with tumour immune evasion, simultaneous targeting these pathways was predicted to control tumour growth by restoring and enhancing anti-tumour immune responses [2,4].

References
1. Gatti-Mays ME, Gulley JL. (2018) M7824: A promising new strategy to combat cancer immune evasion. Oncoscience, 5 (11-12): 269-270. [PMID:30652109]
2. Grenga I, Donahue RN, Gargulak ML, Lepone LM, Roselli M, Bilusic M, Schlom J. (2018) Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis. Urol Oncol, 36 (3): 93.e1-93.e11. [PMID:29103968]
3. Jochems C, Tritsch SR, Pellom ST, Su Z, Soon-Shiong P, Wong HC, Gulley JL, Schlom J. (2017) Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824). Oncotarget, 8 (43): 75217-75231. [PMID:29088859]
4. Lind H, Gameiro SR, Jochems C, Donahue RN, Strauss J, Gulley MD, JL, Palena C, Schlom J. (2020) Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. J Immunother Cancer, 8 (1). DOI: 10.1136/jitc-2019-000433 [PMID:32079617]
5. Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C et al.. (2020) Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer, 8 (2). DOI: 10.1136/jitc-2020-001395 [PMID:33323462]

References

1. Gatti-Mays ME, Gulley JL. (2018)
M7824: A promising new strategy to combat cancer immune evasion.
Oncoscience, 5 (11-12): 269-270. [PMID:30652109]

2. Grenga I, Donahue RN, Gargulak ML, Lepone LM, Roselli M, Bilusic M, Schlom J. (2018)
Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis.
Urol Oncol, 36 (3): 93.e1-93.e11. [PMID:29103968]

3. Jochems C, Tritsch SR, Pellom ST, Su Z, Soon-Shiong P, Wong HC, Gulley JL, Schlom J. (2017)
Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).
Oncotarget, 8 (43): 75217-75231. [PMID:29088859]

4. Lind H, Gameiro SR, Jochems C, Donahue RN, Strauss J, Gulley MD, JL, Palena C, Schlom J. (2020)
Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances.
J Immunother Cancer, 8 (1). DOI: 10.1136/jitc-2019-000433 [PMID:32079617]

5. Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C et al.. (2020)
Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies.
J Immunother Cancer, 8 (2). DOI: 10.1136/jitc-2020-001395 [PMID:33323462]