14 Perspectives of Aptamers for Medical Applications
429
leukemia were recruited to be treated with NOXA-12 in combination with bendamustine and rituximab. The results showed NOXA-12 rapidly increase circulating CLL
cells with a peak at 24 h, as well as CXCR4 expression on CLL cells, single-agent
treatment was well tolerated. It did not result in additional toxicity in combination
treatment with bendamustine and rituximab [106].
The preclinical study focus on lymphoma also has excellent advances in targeting
therapy. For example, CD30 is highly expressed on Hodgkin’s lymphoma and
anaplastic large cell lymphoma (ALCL), it provides a possibility for target therapy.
An RNA aptamer [141] targeting CD30 was developed in 2004 in vitro study
showed that siRNA for anaplastic lymphoma kinase (ALK) oncogene complexed
with CD30 could significantly increase the death rate of ALCL cells;a modification
for CD30 nano-complex effectively enhances its ability to selectively kill ALCL
cells [142, 143] without damaging off-target cells. To avoid the shortcoming of RNA
aptamer, such as rapidly digested by serum nucleases, Parekh, P et al.constructed an
ssDNA aptamer [144] targeting CD30, which exhibited a concentration-dependent
promotion of apoptosis in CD30 positive cells instead of negative cells.
Except for aptamers mentioned above, other in vitro experiments on biomarker
targeting malignancy of blood were also processed, including aptamer CD117 and
CD123 for AML; BCR-ABL, β-arrestins for CML; CD20, CD28, BAFF-R, Ig light
chain, Ig heavy chain for B cell lymphoma; CD38, annexin A2 for plasma cell
neoplasms [145].
Aptamer-mediated target therapy presents distinct advantages in hematological
malignancy, compared with traditional chemotherapy. It has a vast spectrum of targets
on cell-surface marker or intracellular oncogenes. It is easy to form complexes with
many substances including chemical drugs, nanoparticles, siRNA, etc. and it has a
high affinity, specificity, and lower immunogenicity.
Although a variety of aptamers have been selected to treat hematological malignancy, most of them are still lying on the bench. The main challenges lie in the intrinsic
properties of the aptamer. Firstly, aptamer is easy to be degraded by nuclease, which
needs to be modified by inserting specific structures into an aptamer to promote its
stability in the blood. Secondly, aptamer has a high renal filtration because of its small
size, which is one of the advantages when referring to cell internalization. Linking to
polymer-like PEG is a common strategy to keep the aptamer; at the same time, these
methods also bring side effects such as cell toxicity arising from the immunogenicity
of PEG.
Another critical obstacle for aptamer from the bench to bed is the characteristic
of homeostasis in the human body. The temperature, PH,osmolality, ion concentration, etc. of the human body are fluctuated with a narrow range. To achieve the
best robustness and effect, in vitro studies would adopt harsh conditions, such as
extremely low/high PH or temperature that would lead to no-effect or lower effects
when aptamer is transferred from bench to bed.
429
leukemia were recruited to be treated with NOXA-12 in combination with bendamustine and rituximab. The results showed NOXA-12 rapidly increase circulating CLL
cells with a peak at 24 h, as well as CXCR4 expression on CLL cells, single-agent
treatment was well tolerated. It did not result in additional toxicity in combination
treatment with bendamustine and rituximab [106].
The preclinical study focus on lymphoma also has excellent advances in targeting
therapy. For example, CD30 is highly expressed on Hodgkin’s lymphoma and
anaplastic large cell lymphoma (ALCL), it provides a possibility for target therapy.
An RNA aptamer [141] targeting CD30 was developed in 2004 in vitro study
showed that siRNA for anaplastic lymphoma kinase (ALK) oncogene complexed
with CD30 could significantly increase the death rate of ALCL cells;a modification
for CD30 nano-complex effectively enhances its ability to selectively kill ALCL
cells [142, 143] without damaging off-target cells. To avoid the shortcoming of RNA
aptamer, such as rapidly digested by serum nucleases, Parekh, P et al.constructed an
ssDNA aptamer [144] targeting CD30, which exhibited a concentration-dependent
promotion of apoptosis in CD30 positive cells instead of negative cells.
Except for aptamers mentioned above, other in vitro experiments on biomarker
targeting malignancy of blood were also processed, including aptamer CD117 and
CD123 for AML; BCR-ABL, β-arrestins for CML; CD20, CD28, BAFF-R, Ig light
chain, Ig heavy chain for B cell lymphoma; CD38, annexin A2 for plasma cell
neoplasms [145].
Aptamer-mediated target therapy presents distinct advantages in hematological
malignancy, compared with traditional chemotherapy. It has a vast spectrum of targets
on cell-surface marker or intracellular oncogenes. It is easy to form complexes with
many substances including chemical drugs, nanoparticles, siRNA, etc. and it has a
high affinity, specificity, and lower immunogenicity.
Although a variety of aptamers have been selected to treat hematological malignancy, most of them are still lying on the bench. The main challenges lie in the intrinsic
properties of the aptamer. Firstly, aptamer is easy to be degraded by nuclease, which
needs to be modified by inserting specific structures into an aptamer to promote its
stability in the blood. Secondly, aptamer has a high renal filtration because of its small
size, which is one of the advantages when referring to cell internalization. Linking to
polymer-like PEG is a common strategy to keep the aptamer; at the same time, these
methods also bring side effects such as cell toxicity arising from the immunogenicity
of PEG.
Another critical obstacle for aptamer from the bench to bed is the characteristic
of homeostasis in the human body. The temperature, PH,osmolality, ion concentration, etc. of the human body are fluctuated with a narrow range. To achieve the
best robustness and effect, in vitro studies would adopt harsh conditions, such as
extremely low/high PH or temperature that would lead to no-effect or lower effects
when aptamer is transferred from bench to bed.