14 Perspectives of Aptamers for Medical Applications
433
This aptamer was constructed into an electrochemical aptasensor to analyze the crude
human blood sample from lung cancer patients (LCP) and healthy people (HP), the
authors used IH-SAB to enhance the sensitivity of aptasensor, which achieved the
detectable protein concentration 100 times lower than traditional ELSAS methods
[178].
Liu’s group [179] identified a 2
-F RNA aptamer (RA16, KD 9 ± 2 nM,) that
specifically binds to NCI-H460, NSCLCS cancer cells, through an in vivo SELEX
in mice using a PEGylated RNA library. RA16 not only can inhibit NCI-H460 proliferation in vitro but also induce growth arrest nearly 50% compared to its control.
It can also enhance the toxicity of epirubicin to the target cells without affecting
normal cells. The combination of RA16 and epirubicin further inhibited the growth
of tumors to 64.38% ± 7.92% when administrated in the H460 xenograft mouse
model. In the following study [180], a truncated fragment of trans-RA16 (S3) was
identified, with a KD of 63.20 ± 0.91 nM. This truncated aptamer can also inhibit
NCI-H460 cell growth by 39.32 ± 3.25% at 150 nM.
These serial studies provide exciting preclinical data that facilitate the development of a novel diagnostic or treatment scheme for NSCLC in clinical settings.
Cancer immune escape plays a critical role in cancer progression. Targeting
immune T cells to control cancer cells to immune escape is an optional strategy
in target therapy. Galectin-1 (Gal-1), a14.5-kDa protein, is a member of the galectin
family of β-galactoside-binding proteins. It is involved in tumor progression and
chemoresistance in several cancers [181, 182]. In lung cancer, Gal-1 activated lung
cancer-associated fibroblasts and impaired T cell differentiation and function [182].
It seems that Gal-1 could be a potential therapeutic target in cancer therapy. Tsai
et al. [183] screen the first Gal-1-DNA targeting aptamer, (AP-74 M-545, KD
3.747 nmol/L), which presents the in vivo tumor suppression effects by reducing
T cell apoptosis. This finding provides preclinical data for targeting Gal-1 to avoid
cancer immune escape.
Gynecological Cancer
Gynecological cancers are those that develop in a woman’s reproductive tract mainly
including cervical, uterine, ovarian, vaginal, and vulvar cancer. Identifying these
cancers at an earlier stage is a critical process for the survival of the patients. Among
available probes to detect and target the cancer cells, the aptamer is efficiently a
probe of high affinity. Different aptamers have been generated against gynecological cancer biomarkers including HE4, CA125, VEGF, OCCA (for ovarian cancer),
EGFR, FGFR1, K-ras (for endometrial cancer), HPV E-16, HPV E-7, HPV E-6,
tyrosine, and kinase (for cervical cancer) and can identify the cancers in woman
reproductive organs. However, only a limited aptamer has preclinical or clinical
usages.
Cancer antigen 125 (CA 125) is a glycoprotein mainly expressed on the cell
surface and released into the blood serum. It elevated to 50% in early-stage ovarian
cancer and reach to over 80% at the advanced stage.
433
This aptamer was constructed into an electrochemical aptasensor to analyze the crude
human blood sample from lung cancer patients (LCP) and healthy people (HP), the
authors used IH-SAB to enhance the sensitivity of aptasensor, which achieved the
detectable protein concentration 100 times lower than traditional ELSAS methods
[178].
Liu’s group [179] identified a 2
-F RNA aptamer (RA16, KD 9 ± 2 nM,) that
specifically binds to NCI-H460, NSCLCS cancer cells, through an in vivo SELEX
in mice using a PEGylated RNA library. RA16 not only can inhibit NCI-H460 proliferation in vitro but also induce growth arrest nearly 50% compared to its control.
It can also enhance the toxicity of epirubicin to the target cells without affecting
normal cells. The combination of RA16 and epirubicin further inhibited the growth
of tumors to 64.38% ± 7.92% when administrated in the H460 xenograft mouse
model. In the following study [180], a truncated fragment of trans-RA16 (S3) was
identified, with a KD of 63.20 ± 0.91 nM. This truncated aptamer can also inhibit
NCI-H460 cell growth by 39.32 ± 3.25% at 150 nM.
These serial studies provide exciting preclinical data that facilitate the development of a novel diagnostic or treatment scheme for NSCLC in clinical settings.
Cancer immune escape plays a critical role in cancer progression. Targeting
immune T cells to control cancer cells to immune escape is an optional strategy
in target therapy. Galectin-1 (Gal-1), a14.5-kDa protein, is a member of the galectin
family of β-galactoside-binding proteins. It is involved in tumor progression and
chemoresistance in several cancers [181, 182]. In lung cancer, Gal-1 activated lung
cancer-associated fibroblasts and impaired T cell differentiation and function [182].
It seems that Gal-1 could be a potential therapeutic target in cancer therapy. Tsai
et al. [183] screen the first Gal-1-DNA targeting aptamer, (AP-74 M-545, KD
3.747 nmol/L), which presents the in vivo tumor suppression effects by reducing
T cell apoptosis. This finding provides preclinical data for targeting Gal-1 to avoid
cancer immune escape.
Gynecological Cancer
Gynecological cancers are those that develop in a woman’s reproductive tract mainly
including cervical, uterine, ovarian, vaginal, and vulvar cancer. Identifying these
cancers at an earlier stage is a critical process for the survival of the patients. Among
available probes to detect and target the cancer cells, the aptamer is efficiently a
probe of high affinity. Different aptamers have been generated against gynecological cancer biomarkers including HE4, CA125, VEGF, OCCA (for ovarian cancer),
EGFR, FGFR1, K-ras (for endometrial cancer), HPV E-16, HPV E-7, HPV E-6,
tyrosine, and kinase (for cervical cancer) and can identify the cancers in woman
reproductive organs. However, only a limited aptamer has preclinical or clinical
usages.
Cancer antigen 125 (CA 125) is a glycoprotein mainly expressed on the cell
surface and released into the blood serum. It elevated to 50% in early-stage ovarian
cancer and reach to over 80% at the advanced stage.