Gamma-delta work makes cautious inroads into the clinic

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TC Biopharm’s treatment of the first patient cohort in a study of OmnImmune (TCB002) marks only the fourth human trial of gamma-delta cells in the West. There might be more, as the UK company stresses that the trial is intended as a prelude to going into the clinic with a gamma-delta CAR-T cell product – possibly a first – later this year. Gamma-delta T cells have T-cell receptors comprising gamma and delta, rather than the more common alpha and beta, subunits. Since alpha-beta T-cell receptors are responsible for autoimmunity, gamma-delta T cells have low propensity to cause graft-versus-host disease, and might therefore be used off the shelf. Indeed, TC says the purpose of the OmnImmune study is merely to demonstrate the safety of injecting expanded but unmodified, donor-derived gamma-delta T cells into nine acute myelogenous leukaemia subjects. Other clinical trials include those of Gadeta’s TEG001 and an academic trial of OmnImmune, while an Innate Pharma study at Rennes University Hospital was terminated 10 years ago. Clinical work is also under way in China, and the space has seen deals too (Gamma-delta follows financing with consolidation, July 20, 2018).

Selected γδ T-cell players
Company Based in Genetic modification? Notes Lead asset
Gadeta Netherlands Yes: αβ T cells expressing engineered γδ T-cell receptor €7m series A (Baxalta) in 2016; Gilead exclusive buyout option in 2018 TEG001 (phase I)
TC Biopharm UK Not yet, but allogeneic CAR-engineered γδ T cells are planned Deal with Bluebird, $16m up front OmnImmune (phase I)
Incysus US No: expanded allogeneic γδ T cells Leukaemia study filed in May 2018, not under way yet EAGD-T cells (phase I starting May 2019)
Gammadelta Therapeutics UK Not clear; possibly CAR-engineered γδ T cells $100m financing (Abingworth, Takeda); bought Lymphact in 2018 DOT-Cells technology
Immatics Germany Yes: allogeneic engineered T-cell receptor γδ T cells $58m funding 2017, $54m Genmab deal covering bispecifics in 2018  ACTallo technology
Puretech Health US Not clear Formed Nybo Therapeutics subsidiary in 2017 Unknown
Medinet Japan Not clear Contract manufacturer carrying out γδ T-cell expansion, named in patents Unknown
Source: company filings.

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