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B and T lymphocyte attenuator   Click here for help

GtoPdb Ligand ID: 4891

Abbreviated name: BTLA
Synonyms: B- and T-lymphocyte attenuator  | B- and T-lymphocyte-associated protein | CD272
Immunopharmacology Ligand
Compound class: Endogenous peptide in human, mouse or rat
Comment: BTLA is a negative immunomodulator. Interaction of BTLA with TNFRSF14 (HVEM) constitutes an immune checkpoint which inhibits T cell-mediated immune responses. Dysregulated BTLA expression contributes to immunosuppression and progression of some cancers [3-6] by enabling tumour immune evasion. Immunotherapeutics that block the BTLA-HVEM checkpoint offer potential as anti-tumour agents [8-9]. In the setting of inflammatory diseases anti-BTLA antibodies can induce inhibitory signalling and block T cell activation, thus reducing pro-inflammatory cytokine secretion [1].

Several anti-BTLA monoclonals have been progressed to clinical trials. Examples include:
Radanstobart (HFB200603, HiFiBiO; Phase 1 NCT05789069, solid tumours) [2]
Zadoprubart (ANB032, AnaptysBio; Phase 2 NCT05935085, atopic dermatitis; terminated due to insufficient efficacy) [1]
Venanprubart (LY3361237; development for autoimmune conditions terminated at Phase 2)
Tifcemalimab (JS004, icatolimab; Junshi Biosciences for advanced/metaststic solid tumours) [7]
GS-0272 (formerly MB272; Phase 1 NCT06031415 for rheumatoid arthritis was terminated).
Species: Human
References
1. Dahl M, Hsu M, Schendel C, Haines C, Soroosh P, Parmley S, Hare E. (2024)
ANB032, a novel BTLA agonist monoclonal antibody, reduced T cell proliferation, inflammatory cytokine secretion and prevented graft versus host disease in a mouse model.
J Immunology, 212 ((1_Supplement)). DOI: 10.4049/jimmunol.212.supp.0518.5691
2. hifibio. 
HFB200603: BTLA Antagonist.
Accessed on 11/03/2025. Modified on 11/03/2025. hifibio.com, https://hifibio.com/pipeline/programs/hfb200603/
3. Hu X. (2024)
The role of the BTLA-HVEM complex in the pathogenesis of breast cancer.
Breast Cancer, 31 (3): 358-370. [PMID:38483699]
4. Kong X, Zhang J, Chen S, Wang X, Xi Q, Shen H, Zhang R. (2024)
Immune checkpoint inhibitors: breakthroughs in cancer treatment.
Cancer Biol Med, 21 (6): 451-72. [PMID:38801082]
5. Miyashita H, Bevins NJ, Thangathurai K, Lee S, Pabla S, Nesline MK, Glenn ST, Conroy JM, DePietro P, Rubin E et al.. (2024)
The transcriptomic expression pattern of immune checkpoints shows heterogeneity between and within cancer types.
Am J Cancer Res, 14 (5): 2240-2252. [PMID:38859855]
6. Ries J, Trumet L, Hahn A, Kunater L, Lutz R, Geppert C, Kesting M, Weber M. (2024)
The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators.
Int J Mol Sci, 25 (12). [PMID:38928307]
7. Song Y, Ma J, Zhang H, Xie Y, Peng Z, Shuang Y, Li F, Li Y, Yang H, Zou L et al.. (2025)
Tifcemalimab as monotherapy or in combination with toripalimab in patients with relapsed/refractory lymphoma: a Phase I trial.
Nat Commun, 16 (1): 4559. [PMID:40379637]
8. Wojciechowicz K, Kuncewicz K, Rutkowski J, Jassem J, Rodziewicz-Motowidło S, Wardowska A, Spodzieja M. (2024)
Targeting BTLA with the peptide inhibitor HVEM(14-39) - A new way to restore the activity of T cells in melanoma.
Biomed Pharmacother, 175: 116675. [PMID:38733770]
9. Wojciechowicz K, Spodzieja M, Wardowska A. (2024)
The BTLA-HVEM complex - The future of cancer immunotherapy.
Eur J Med Chem, 268: 116231. [PMID:38387336]