Autologous Foxp3+ polyTreg adoptive transfer immunotherapy: phase I study

2nd paper in this week's Science Translational Medicine is more directly related to Foxp3⁺ T_regs. Here, the authors has conducted phase I, dose-escalation study in recent onset T1D patients (16 participants) to determine safety of adoptive transfer of ex-vivo expanded autologous polyclonal Foxp3⁺ T_regs cells.

Unlike CAR-T therapy with its bulk PBMCs as its main ex-vivo target population, working with flow sorted polyT_regs cells is more demanding and few institutions are equipped to conduct such GMP-grade clinical trials. As shown in Table 3, there is variability in ex-vivo expansion potential between polyT_regs cells derived from various donors [since no "healthy" control subjects were included in this trial, it is no clear whether this level of expansion of polyT_regs cells is specific for T1D patients].

The authors conducted several functional/marker analysis on 14-day expanded polyT_regs cells. These results revealed that expanded polyT_regs cells retain the same degree of (a) demethylation at Foxp3 locus, (b) they showed improved phosphorylation of STAT5 in response to IL-2, (c) displayed improved suppressive potential in an in vitro proliferation assay.

After adoptive transfer of expanded polyT_regs cells patients were monitored for any [metabolic] abnormalities. There were few adverse events related to T1D metabolic events that probably were not caused by polyT_regs cell transfer per se. However, due to small sample size, adoptive transfer of polyT_regs cells did not reveal any substantial improvement of T1D in recipients either [though transferred polyT_regs cells labeled with [6,6-²H₂]glucose were detected up to 1 year in cohort 3 and 4].

In summary, this phase I study of polyT_regs cells confirms feasibility of adoptive transfer immunotherapy with Foxp3⁺ polyT_regs cells. In general, it is my opinion that only by understanding Foxp3⁺ T_regs cells can we truly unlock the full benefits of immunotherapy for cancer, allergy and autoimmune diseases.

David Usharauli