New targeting approach to treat T-cell lymphomas published

Clinical-stage biopharmaceutical company, Autolus has announced the publication of an article detailing a unique targeting strategy for the treatment of patients with T-cell lymphomas in Nature Medicine.

“T-cell lymphomas are blood cancers characterised by a very poor prognosis, particularly after a patient relapses following initial treatment. Unlike other blood cancers, it is not possible to use agents that totally remove all of the cell-type containing the malignancy as T-cells are needed to fight infections,” said Dr Julie Vose, chief, Division of Haematology/Oncology, Professor of Medicine, Nebraska Medical Center. “This highly innovative approach addresses this challenge elegantly by selectively removing the portion of the T-cells containing the cancer while leaving a healthy T-cell population intact to provide protection against infection. Consequently, it offers real promise as a potential treatment for this aggressive form of cancer.”

In the article, Dr Paul Maciocia and his co-authors, describe a new targeting approach that is based on the mutually exclusive expression of two subtypes of the T-cell receptor beta chain (TRBC1 and TRBC2). Both these subtypes are found in normal cells, however, either TRBC1 or TRBC2 are expressed in T-cell lymphoma cells as a result of their clonal origins and evolution.

The team developed anti-TRBC1 CAR T-cells, which recognise and kill normal and malignant TRBC1 but not TRBC2 T-cells in mouse models of T-cell Lymphoma, as proof-of-concept for anti-TRBC immunotherapy. This work forms the scientific basis for AUTO4, a unique CAR T-cell product developed by Autolus to target TRBC1, which is due to enter the clinic in the coming months.

The full manuscript ‘Targeting T-cell receptor β-constant for immunotherapy of T-cell malignancies’ can be found in the December 2017 issue of Nature Medicine.