Table 3.

Aptamers selected by cell-based SELEX on pre-identified tumor cell-surface biomarkers.

Biomarker	Aptamer Library	Number of Variable Positions	KD Range	Number of Positive Selection Rounds (selection method) 1	Cells Used for Positive Selection	Cells Used for Counter-SELEX	Applications	References
Tyrosine kinase receptors
EGFRvIII	DNA	30	0.62–37.57 nM	14	U87-EGFRvIII, U87-MG, GBM cells overexpressing EGFRvIII	U87-MG	Potential applications: delivery of chemical drug and diagnosis	[117]
EGFRvIII	DNA	40	3–16 nM	11	U87-MG, GBM cells overexpressing EGFRvIII	U87-MG	Imaging (radiolabeled 188Re, in vivo) Potential applications: diagnosis in stratifying patient and monitoring treatment	[118]
HER-2	RNA	40	94.6 nM	20	HER-2-overexpressing SK-BR-3 cell line	MDA-MB-231, a HER-2-underexpressing breast cancer cell line	Potential application: therapy	[113]
HER-2	2′F-RNA	20	46–82 nM	9 (cell-internalization SELEX)	N202.1A mammary carcinoma clonal cell lines expressing high levels of surface HER-2/neu.	N202.1 E clonal cell line has no detectable surface expression of the HER2/neu oncoprotein.	Drug delivery (Bcl-2 siRNA) Induces chemosensibilisation and reduces drug resistance	[100]
HER-2	DNA	50	Not documented	4 rounds	Cleared extract of ErbB-2-overexpressing N87 cells	Not documented	Acceleration of ErbB-2 degradation in lysosomes Inhibition of growth of tumor cell in vitro and tumor mass in vivo	[116]
HER-2	DNA	30	5–23 nM	8 rounds of protein SELEX followed by 7 rounds of cell -SELEX (hybrid-SELEX)	HER-2 overexpressed in SKOV3 ovarian cancer cells	No cells	PET imaging (radio labeled, in vivo)	[109]
HER-2	DNA	40	Not documented	16	HER2- overexpressing breast cancer cell line, SK-BR3	HER2 negative breast cancer cell line, MDA-MB468	Development of a new method to monitor the enrichment of aptamers in a given round of cell-SELEX	[114]
Receptor tyrosine kinase-RETC634Y	2′F RNA	50	Tens of nM	15 rounds of selection on cells, followed by 7 rounds on purified protein (hybrid-SELEX)	RETC634Y mutant receptor expressed in PC12 cells (PC12/MEN2A)	PC12	Potential applications: diagnosis, imaging and therapy	[108]
Neurotrophin receptor TrkB	2′F RNA	20	2 nM	4 (cell-internalization SELEX)	TrkB-expressing HEK cells	HEK	Neuroprotective effects Potential in therapy for neuro degenerative disease	[119]
Other kinase receptors
TGFβ III receptor	2′F RNA	60	1 nM	11	TGFβ III receptor ectopically expressed on CHO-K1 cells	CHO-K1	Potential application: therapy through inhibition of TGFβIII receptor	[102]
Transferrin receptors (TfR)
CD71	2′F-RNA	50	nM range	4 rounds of protein-SELEX on the His-tagged recombinant protein and 1 round on cells (hybrid SELEX combined with cell-internalization SELEX)	HeLa cells, a human cervical cancer cell line known to express TfR	NO cells	Delivery of siRNA Targets cell in liposomes	[94]
ATP-binding cassette (ABC) transporters
Multidrug resistant-associated protein 1-MRP1	2′F-RNA	25	50 nM	10 rounds of peptide-SELEX followed by 1 round of cell-SELEX (hybrid-SELEX)	chemotherapy-resistant tumor cell line that has high MRP1 expression (H69AR)	Parental cell line H69	Reduction of cell growth in vitro and improved survival in vivo	[111]
Cell adhesion molecules
Epithelial cell adhesion molecule-EpCAM (CD326)	DNA	40	μM range	7 (FACS-SELEX)	EpCAM over-expressed in HepG2 cells	HepG2 cells	Potential application: stem cell marker	[120]
Integrin α6β4	DNA	39	139 nM	5 rounds of cell-SELEX followed by 7 rounds of protein-SELEX (hybrid-SELEX)	PC-3 cells	PC-3 β4 integrin (ITGB4) knockdown cells	Imaging (confocal) Potential application: drug delivery	[110]
Integrin αv	RNA	35 & 40	359–408 nM	13 (Isogenic cell-SELEX)	Human HEK293 cells manipulated to generate positive αv selection cells by overexpressing ITGAV	Human HEK293 cells depleted in ITGAV with microRNA-mediated silencing.	Potential application: targeting channels, transporters…	[112]
Fc receptors
CD16α	DNA	40	6–429 nM	9 rounds of protein-SELEX and 6 rounds of cell-SELEX (hybrid-SELEX)	CD16_-6His and CD16_ Val-158 or Phe-158 alloforms expressed on recombinant Jurkat cells	Jurkat E6.1 cell line	ADCC (tumor cell lysis)	[64]
Surface transmembrane glycoproteins
CD133	2′F RNA	40	Not determined	6	HEK293T expressing CD133	His-tagged irrelevant protein expressed in HEK293T	Potential application: target cancer stem cells and molecular imaging	[121]
CD30 TNFRSF8	DNA	30	nM range	20 rounds of cell-SELEX followed by 5 rounds on purified His-tagged CD30 protein (hybrid-SELEX)	CD30-positive K299 T-cells lymphoma	Jurkat cells	Potential application: therapy	[115]

¹ Selection method is specified if it is different from classical cell-SELEX.