Highlights
Takeda Pharmaceutical will buy GammaDelta Therapeutics, which specializes in the development of immunotherapy based on gamma delta (γδ) T cells. The Japanese pharmaceutical giant will take over the British biotech startup under the terms of a deal formalized in 2007. At the time, $100 million was invested in GammaDelta.
γδ T cells are a small population of cells with a modified T-cell receptor (TCR) formed by γ and δ subunits, rather than α and β subunits as with most other T cells. This allows them to recognize antigens in situ, i.e. without their presentation by MHC molecules on antigen-presenting cells (APCs). As a result, a very rapid immune response is realized. Human γδ T cells are unique in that they specifically and rapidly respond to a set of non-peptide phosphorylated isoprenoid precursors, commonly called phosphoantigens, which are produced by virtually all living cells, including cancer cells.
Independence from MHC makes it possible to talk about treatment without reference to the specific features of a particular patient’s immune system — autologous cell therapy turns into allogeneic therapy. γδ T cells do not require prior antigen priming, have equal potential to destroy tumor cells with low mutation load, and are less susceptible to therapeutic resistance.
Details
The GammaDelta’s technology platform addresses γδ T cells, which have a variable TCR segment Vδ1. This subset of cells has been demonstrated in preclinical studies to be suitable for the treatment of cancer. In addition, Vδ1+ γδ T cells can be useful for blood cancer patients undergoing autologous stem cell transplantation in order to prolong long-term survival and reduce the risk of graft-versus-host disease. There are prerequisites for their use in the treatment of infectious diseases (CMV, HIV) and inflammatory bowel diseases.
Takeda will gain control of an allogeneic platform of Vδ1+ γδ T cells derived from donor skin or blood, as well as its very early developmental variant involving chimeric antigen receptor (CAR) inclusion.
In September 2021, GammaDelta began a phase 1 clinical trial of NCT05001451 experimental GDX012 (allogeneic enriched culture of Vδ1+ γδ T cells) among adult patients with acute myeloid leukemia (AML) in complete response (CR) status and with minimal residual disease (MRD) to evaluate the safety, tolerability, and anti-leukemia activity of the trial therapy.
In March 2021, Takeda bought Maverick Therapeutics in order to improve T-cell redirection therapies to fight cancer through its COBRA T-cell engager platform. Among the main candidate drugs are TAK-186 (MVC-101) and TAK-280 (MVC-280) against solid tumors expressing EGFR and B7H3, respectively.
Extras
Unlocking the power of Vδ1+ γδ T lymphocytes to transform cancer cell therapy. Nature, Biopharma Dealmakers. [source] [PDF]