Figure 3.
ALKS 4230 expanded fewer suppressive Tregs and expanded and activated NK cells to a greater extent than rhIL-2 in human samples. Selected lymphocyte subsets identified by flow cytometry were quantified in PBMCs expanded from healthy donors (HD), individuals diagnosed with advanced melanoma (MEL), or renal cell carcinoma (RCC), with 0.5 nM rhIL-2 or 0.5 nM ALKS 4230 (n=4 for each group). Proportions of CD4+CD25+CD127low/- Tregs from (A) individual samples and the (B) average proportion by treatment. (C) Percentages of ICOS+ Tregs were greater in rhIL-2 expanded cultures. NK cell proportions from (D) individual samples and (E) grouped by treatment. Percentages of activated NK cells that expressed (F) CD25 and (G) CD69 were greater in ALKS 4230-expanded cultures. (H) The proportion of central memory CD8+ T cells were similar in ALKS 4230 and rhIL-2-expanded cultures. The ratios of selected lymphocyte populations to Tregs were calculated in PBMCs expanded from healthy donors, and individuals diagnosed with advanced melanoma or RCC. (I) CD56+CD16- NK:Treg and (J) central memory CD8+ T:Treg ratios were all significantly greater in ALKS 4230-expanded cultures. Statistical significance between treatment groups was determined by paired T tests. *p<0.01, **p<0.001, ***p<0.0001. ICOS+, inducible T cell costimulator-positive; IL-2, interleukin-2; NK, natural killer; PBMCs, peripheral blood mononuclear cells; rhIL-2, recombinant human IL-2; Tregs, regulatory T cells.
