Adaptimmune just presented a poster at the society for Immunotherapy of Cancer annual meeting 2016 where they provide some encouraging insight into their work with second generation engineerd T-cells. In a poster presentation entitled, “Engineering 2nd generation SPEAR T-cells to overcome TGF-Beta-mediated immunosuppression for adoptive cell therapy,” Andrew Gerry, Ph.D. of Adaptimmune presented preclinical data regarding the development of this second generation SPEAR T-cell:
NY-ESO SPEAR T-cells have shown promising activity in clinical trials for both solid and liquid tumors. However, the depth and durability of response may potentially be affected by inhibitory factors in the tumor microenvironment;
One such factor is an inhibitory cytokine known as TGF-Beta that inhibits many T‑cell functions including proliferation, cytotoxicity, and cytokine production. Truncation of the intracellular signaling domain of the TGF-Beta receptor produces a dominant negative form of this receptor (dnTGFBetaRII), and data from the literature indicate that expression of this dominant negative receptor negates the inhibitory effects of TGF-Beta;
Adaptimmune engineered a second generation NY-ESO SPEAR T-cell co-expressing dnTGFBetaRII to produce resistance to TGF-Beta immunosuppression, and;
Data indicate that these second generation NY-ESO SPEAR T-cells co-expressing dnTGFBetaRII are resistant to inhibition by TGF-Beta in vitro.
Probably this is just a first step to make engineer T cells more efficient in such a way that they can counteract the inhibitory mechanisms of malignant cancer cells. We’ll be closely watching Adaptimmune’s progress with their SPEAR program.