Saturday, November 28, 2015

Autologous Foxp3+ polyTreg adoptive transfer immunotherapy: phase I study

Unlike CAR-T therapy with its bulk PBMCs as its main ex-vivo target population, working with flow sorted polyTregs 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 polyTregs 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 polyTregs cells is specific for T1D patients].

The authors conducted several functional/marker analysis on 14-day expanded polyTregs cells. These results revealed that expanded polyTregs 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 polyTregs cells patients were monitored for any [metabolic] abnormalities. There were few adverse events related to T1D metabolic events that probably were not caused by polyTregs cell transfer per se. However, due to small sample size, adoptive transfer of polyTregs cells did not reveal any substantial improvement of T1D in recipients either [though transferred polyTregs 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 polyTregs cells confirms feasibility of adoptive transfer immunotherapy with Foxp3+ polyTregs cells. In general, it is my opinion that only by understanding Foxp3+ Tregs cells can we truly unlock the full benefits of immunotherapy for cancer, allergy and autoimmune diseases.

David Usharauli

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