Table 3.

Summary of recent anti-innate immune preclinical and clinical trials in MDS

Targeted molecule	Agent	Status	Potential therapeutic effect	References
TLR2/JMJD3	shRNA	Preclinical	Improvement of erythroid differentiation of MDS BM CD34+ cells	De Luca et al.,64 Perkins et al.69
MyD88	Inhibitory peptide	Preclinical	Improvement of erythroid differentiation of MDS BM CD34+ cells	Dimicoli et al.56
IL-8	Neutralizing antibody	Preclinical	Improvement of erythroid differentiation of MDS BM CD34+ cells	Dimicoli et al.56
IL-8 receptor	SB-332235	Preclinical	Reduction of growth and colony formation in MDS BM CD34+ cells	Giricz et al.115
IRAK1	RNAi and specific inhibitor molecule	Preclinical	Induction of apoptosis and impairment of clonal generation in MDS BM cells	Dimicoli et al.,56 Rhyasen et al.57
p38 MAPK	SCIO-469	Preclinical	Enhancement of hematopoiesis and reduction of apoptosis in MDS BM CD34+ cells, anti-inflammatory effects in BM stromal cells	Navas et al.,44 Navas et al.114
p38 MAPK	ARRY614	Phase I	Hematological improvement in patients who previously failed azanucleoside treatment	Sekeres et al.116
TLR2	OPN-305	Entering phase II	Improvement of erythroid differentiation of MDS BM CD34+ cells	Reilly et al.117
TGF-β receptor I kinase	LY-2157299	Recruiting for phases II/III	Improvement of MDS BM progenitor colony formation in vitro and in vivo, stimulation of hematopoiesis	Zhou et al.118
IDO1	INCB024360	Phase II	Enhancement of Tand NK cell-mediated immune response against the malignant clone; expansion of granulocytic/erythroid progenitors	Berthon et al.,34 Liu et al.119

Abbreviations: BM, bone marrow; IL-8, interleukin-8; MDS, myelodysplastic syndrome; TGF-β, transforming growth factor beta; TLR, Toll-like receptor.