Autolus announces publication in Nature

14th November 2017

Autolus Announces Publication of a Unique Therapeutic Approach for Treatment of Patients with T-Cell Lymphomas in Nature Medicine

London, 14 November 2017

Autolus Limited, a clinical-stage biopharmaceutical company focused on the development and commercialisation of next-generation engineered T-cell therapies, today announced the publication of an article in Nature Medicine describing a unique targeting strategy for the treatment of patients with T-cell lymphomas.

T-cell lymphomas are a family of rare and aggressive cancers for which there are few treatment options. A key challenge of treating these cancers has been to identify a target that would allow the elimination of T-cell lymphoma while sparing healthy T-cells, as these play an essential role in providing protection against infections.

Dr Paul Maciocia and his co-authors* describe a new targeting approach based on the mutually exclusive expression of two subtypes of the T-cell receptor beta chain (TRBC1 and TRBC2). Normal T-cells contain both TRBC1 and TRBC2 compartments whereas T-cell Lymphoma cells express only TRBC1 or TRBC2 due to clonal origin and evolution of those cancerous cells.

As proof of concept for anti-TRBC immunotherapy, 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. Unlike non-selective approaches targeting the entire T-cell population, this approach eradicates a portion of T-cells containing the malignancy while preserving a healthy T-cell sub-population to preserve cellular immunity.

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 – http://www.nature.com/articles/doi:10.1038/nm.4444

“T-cell lymphomas are blood cancers characterized 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. 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.”

Commenting on the publication, Dr Julie Vose, Chief, Division of Hematology/ Oncology,Professor of Medicine, Nebraska Medical Center