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Microbes & Immunity The feature of bladder cancer stem cells

BC mouse models. They treated the mice with anti-human Researchers at Kunming Medical University, led by Yujin
CD47 antibodies and IgG antibodies (control). The results Chen, conducted hybridoma experiments using EJ cells
showed that in the control group, 10 mice (out of 10) as an immunogen and successfully generated the mouse-
developed 24 lymph node metastases, and 8 mice (out of derived monoclonal antibody KMP1. This antibody
10) developed 37 lung metastases. In the CD47-treated recognized the cell surface antigen CD44, specifically
group, only one mouse developed a single lymph node binding to BC cells, demonstrating its potential for specific
metastasis (1/10), and three mice developed isolated lung and targeted therapy against BCSCs. Compared to the
micro-metastases (3/10). Furthermore, CD47 treatment control group, KMP1 reduced the number of cell colonies
significantly inhibited the growth of CIS. These findings formed by EJ cells from 322 ± 5.5 to 98 ± 8.8, significantly
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indicate that CD47 is an ideal target for treating BC. decreased migration, and reduced adhesion rates to 63%.
Near-infrared photoimmunotherapy (NIR-PIT) is In vivo experiments demonstrated that the growth rate of
a localized molecular cancer therapy that combines a tumors in mice treated with KMP1 significantly slowed
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photosensitizer antibody conjugate and light energy. down, with a tumor suppression rate of 67.11%. These
results suggest that KMP1 could serve as a potential targeted
IRDye700 (a near-infrared light-activated hydrophilic therapy for BC. Further development of humanized KMP1
phthalocyanine dye) generates reactive oxygen species
and singlet oxygen, leading to cell rupture and necrosis. antibodies, as well as their conjugation with drugs, is
+
Researchers at Stanford University, led by Bernhard necessary for targeted treatment against CD44 BCSCs.
Kiss, conjugated IRDye700 with CD47 antibodies and Beyond its role as a surface marker for BCSCs, CD44
applied NIR-PIT for BC treatment. When human BC significantly influences the invasion and migration abilities
cell lines UMUC3, 639V, and HT1376 were incubated of BC. Targeted reduction in CD44 expression can lead
with CD47-IR700 and exposed to radiation, NIR-PIT to effective BC treatment. In pursuit of this potential
increased cell death in a light-dose-dependent manner. therapeutic approach, researchers led by Yisi Luo from
At the maximum irradiation level of 40 J/cm , over 90% New York University have proposed that isothiocyanate
2
of 639V and UMUC3 cells, and over 50% of HT1376 cells (ISO) exhibits this effect. ISO significantly inhibits CD44
underwent apoptosis. Mice-bearing tumors were subjected expression in a dose- and time-dependent manner in the
to combined treatment with anti-CD47-IR700 and NIR-PIT human BC cell line T24T, thereby suppressing the stemness
once a week. Compared to the control group and the group features of BCSCs and the invasive abilities of BC. ISO
treated only with anti-CD47-IR700, mice treated with anti- achieved the reduction of CD44 transcription levels by
CD47-IR700 combined with NIR-PIT showed significantly directly inhibiting the binding of the transcription factor
slowed tumor growth and significantly prolonged survival. SP1 to the CD44 promoter region, leading to weakened
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These findings indicate that NIR-PIT is a feasible targeted transcription of CD44. In addition, ISO induces dicer,
treatment method, and its efficacy could be enhanced by promoting the maturation of miR-4295, which then
selecting monoclonal antibodies with higher specificity. inhibits the translation of USP28 by targeting its 3’UTR
region and subsequently accelerates the degradation of
However, the expression of CD47 on the red blood
cells and circulating hematopoietic stem cells presents CD44. ISO suppresses CD44 expression through both
protein and transcriptional levels. Combining ISO with
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a significant hurdle to its clinical translation. 130,131 Due other therapeutic methods holds promising prospects,
to safety concerns and poor efficacy, CC-90002, a CD47 contributing to the complete eradication of BC and
antibody, had to terminate its clinical trials prematurely reducing the recurrence rate.
(NCT02641002). Several efficient approaches have
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emerged to address this issue. First, the limited expression 4. Conclusion and prospect
of SIRPα (CD47 ligand) in tissues makes it a potential
target for reducing toxicity. Second, bispecific antibody Understanding the mechanisms behind BCSCs’
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is another method for decreasing toxicity by enhancing maintenance of stemness and drug resistance is a
target efficiency. The other target of bispecific antibodies prerequisite for improving treatment efficacy. Furthermore,
usually include GPC3, PD-L1, etc. 133,134 as the characteristics of the metabolomic reprogramming
of BCSCs are gradually uncovered, more feasible targets
3.8.4. CD44 for future therapy will emerge.
CD44, serving as a marker for BCSCs, possesses In addition to intrinsic signaling pathways,
extracellular, transmembrane, and intracellular domains, extracellular cues from the tumor microenvironment
facilitating its binding with various ligands and rendering are indispensable for the maintenance of BCSCs. The
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it highly promising for targeted therapy against BCSCs. tumor microenvironment includes diverse immune cell

Volume 1 Issue 1 (2024) 41 doi: 10.36922/mi.2377