On March 11, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Blood Cancer Journal entitled ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry (Press release, Autolus, MAR 11, 2024, View Source [SID1234641026]).’
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Diagnosing leukemic T-cell malignancies poses challenges due to their resemblance to reactive T-cells. In the paper published by Pedro Horna of Mayo Clinic in collaboration with Autolus, the authors introduce a unique approach for identifying T-cell neoplasms by flow cytometry1. This method adopts the recently described monoclonal antibodies targeting TRBC1 and TRBC22, 3, to assess for TRBC-restriction as a surrogate of clonality. The strategy mirrors the routine and broadly adopted analysis of kappa and lambda immunoglobulin chain restriction for the identification of B-cell malignancies.
This innovative and simple strategy to detect clonal expansion of T-cells by flow cytometry has the potential to facilitate the development of more comprehensive diagnostic panels that can be seamlessly integrated into existing screening protocols, obviating the need for separate T-cell clonality assessments. Autolus is working with world leading flow cytometry companies, including Beckman Coulter Life Sciences, BD (Becton, Dickinson and Company) and Thermo Fisher Scientific, in order to enable the development and distribution of diagnostic panels based on these unique TRBC1 and TRBC2 antibodies.
Advancements in diagnostic approaches for T-cell malignancies, coupled with the development of TRBC1 and TRBC2-directed CAR T cell therapeutics4, may contribute to the improvement of therapeutic strategies in this area of unmet clinical need.
1. Horna et al, Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry. Blood Cancer J. 14, 34 (2024). | doi: 10.1038/s41408-024-01002-0
2. Maciocia et al, Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med 23, 1416–1423 (2017) | doi: 10.1038/nm.4444
3. Ferrari et al, Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies. Nat Commun 15, 1583 (2024) | doi: 10.1038/s41467-024-45854-3
4. Cwynarski et al, First in human study of AUTO4, a TRBC1-Targeting CAR T cell therapy in refractory T cell lymphoma. Hematol Oncol 41, 80–81 (2023) | doi: 10.1002/hon.3163_44