Promising new CAR-T therapy able to target T-cell lymphoma

Dr Martin Pule, CSO of Autolus, on whose work the CAR T therapy is based IMAGE: UCL

The CAR-T space has progressed rapidly over the last few years, culminating in FDA approvals for Novartis and Gilead to treat B-cell lymphomas; however, work conducted by Autolus has potentially opened a new therapeutic pathway for the treatment of T-cell lymphoma.

Therapies for T-cell lymphoma are notoriously difficult to develop because any treatment targeting T cells damages the body’s key line of defence against illness. On top of this, the T cell version of lymphoma is far more aggressive than the B-cell version, though more infrequently found.

Autolus has managed to find a potential workaround to be able to treat individuals with T-cell lymphoma by being discovering how to specifically target the cancerous T cells whilst leaving the healthy T cells to maintain the body’s protection against illness.

Research found that there are two subtypes of the T-cell receptor beta chain, TRBC1 and TRBC2; healthy T cells express both of these subtypes whereas cancerous T cells only one or the other, due to clonal origin.

This allowed Autolus to conduct a proof of concept for anti-TRBC immunotherapy by developing anti-TRBC1 CAR T-cells. It was found, in mouse models, that the CAR T-cells were able to kill normal and malignant TRBC1 but without damaging TRBC2 T-cells.

Dr Julie Vose, Chief, Division of Hematology/ Oncology,Professor of Medicine, Nebraska Medical Center said:

“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.”

Autolus revealed that it plans to enter the clinic to test the therapy in humans in the coming months. A certain degree of caution should still be applied to such promising research, as numerous CAR T therapies struggled with serious safety issues. However, if Autolus can maintain consistent results through early-stage trials, it could generate serious interest as a potential acquisition.

The company only recently completed an $80 million funding round, with investment firm Syncona plumping $30 million on the potential of the company.

Ben Hargreaves