Therapeutic antibodies against cancer stem cells: a promising approach

Sneha, Smarakan; Nagare, Rohit P.; Priya, Syama Krishna; Sidhanth, Chirukandath; Pors, Klaus; Ganesan, Trivadi S.

doi:10.1007/s00262-017-2049-0

Cited by 13 publications

(7 citation statements)

References 115 publications

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“…Different drugs, such as trastuzumab, lapatinib, and pertuzumab, have been developed in order to interfere with the EGF-HER2 pathway. In particular, trastuzumab is a monoclonal antibody that specifically binds HER2 receptor, and it is the most common drug used in the targeted therapy against HER2-positive breast cancers 5 . Studies with trastuzumab showed as this drug is able to reduce the risk of cancer reoccurrence in early-stage HER2-positive breast cancers, and to improve the overall survival in metastatic late-stage ones 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Activated Piezoelectric Nanoparticles Inhibit Proliferation of Breast Cancer Cells

Marino

Battaglini

Pasquale

et al. 2018

Sci Rep

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A nanotechnology-based approach for the inhibition of breast cancer cell proliferation is proposed. The innovative solution consists in a platform based on biocompatible piezoelectric nanoparticles able to target and remotely stimulate HER2-positive breast cancer cells. The anti-proliferative effects of the ultrasound-driven piezoelectric nanoparticle-assisted stimulation significantly reduced the proliferation by inducing the cell cycle arrest. Similarly to a low-intensity alternating electric field, chronic piezoelectric stimulation resulted able to inhibit cancer cell proliferation by upregulating the expression of the gene encoding Kir3.2 inward rectifier potassium channels, by interfering on Ca2+ homeostasis, and by affecting the organization of mitotic spindles during mitosis. The proposed platform, even if specific for HER2-positive cells, shows huge potential and versatility for the treatment of different type of cancers.

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Section: Introductionmentioning

confidence: 99%

Ultrasound-Activated Piezoelectric Nanoparticles Inhibit Proliferation of Breast Cancer Cells

Marino

Battaglini

Pasquale

et al. 2018

Sci Rep

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“…A another option is to use monoclonal antibodies to target these CSC's. This has already been the subject of several studies [18][19][20]. This new research shows that there is a potential to combine conventional chemotherapy with SB administration for a synergistic and effective treatment that does not produce adverse reactions.…”

Section: Discussionmentioning

confidence: 87%

Initial Effects of the SB Natural Anticancer Drug on the Number of NK Cells, CD4+ and CD8+ T Lymphocytes in Human Peripheral Blood

Lee¹

2018

JCTR

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Most anticancer drugs produce cytotoxicites in cancer cells, but also generate effects in normal cells that create undesirable side effects, especially for immune functioning cells which have already been suppressed by cancer invasion or biological effects. The SB natural anticancer drug is a root extract of the Pulsatilla koreana plant that has been used in Korea as an effective anticancer agent for more than 20 different malignant tumors without triggering significant adverse reactions. We investigated the effects of the SB anticancer drug on human immune cells in cancer patients. 24 consecutive patients, with histologically proven cancers, received SB drug treatments and 20 control patients did not receive SB administrations. Both groups were immunologically tested before and after their SB treatments for 14 days and then weekly for the 3 rd , 4 th , 5 th and 6 th weeks thereafter. The total number of white blood cells with differential counts including monocytes and lymphocytes were checked. Immunoassay and flow cytometry were used to analyse CD4 and CD8 T cell percentages, total cell counts with their ratios, as well as CD16/56 natural killer cell percentages and cell counts. Total white blood cell counts normalized within 10 days after the SB drug administrations. The total lymphocyte counts were slightly increased, but remained within normal parameters. CD4 and CD8 T cells, as well as CD 16/56 NK cell percentages, became normal within 10 days; their total cell counts were initially increased (26.3%, 45.2%, and 16.7%, respectively) and then became normal. The SB drug was found to be effective cytoapoptotically and was also effective for immune cell recovery in cancer patients in their initial period of the SB drug treatment. These were patients who had already had a bone marrow suppression by cancer invasion and/or prior chemotherapy.

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“…The cancer stem cells in the spheres are highly resistant to death by chemotherapeutic drugs [35,36]. To further validate the role of pS14-WWOX in supporting cancer survival, we measured the extent of cell death in the 4T1 breast cancer stem cell spheres for their uptake of PI, as determined by time-lapse microscopy [28,33,37,38].…”

Section: Resultsmentioning

confidence: 99%

WWOX Possesses N-Terminal Cell Surface-Exposed Epitopes WWOX7-21 and WWOX7-11 for Signaling Cancer Growth Suppression and Prevention In Vivo

Wang

Nagarajan

et al. 2019

Cancers

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Membrane hyaluronidase Hyal-2 supports cancer cell growth. Inhibition of Hyal-2 by specific antibody against Hyal-2 or pY216-Hyal-2 leads to cancer growth suppression and prevention in vivo. By immunoelectron microscopy, tumor suppressor WWOX is shown to be anchored, in part, in the cell membrane by Hyal-2. Alternatively, WWOX undergoes self-polymerization and localizes in the cell membrane. Proapoptotic pY33-WWOX binds Hyal-2, and TGF-β induces internalization of the pY33-WWOX/Hyal-2 complex to the nucleus for causing cell death. In contrast, when pY33 is downregulated and pS14 upregulated in WWOX, pS14-WWOX supports cancer growth in vivo. Here, we investigated whether membrane WWOX receives extracellular signals via surface-exposed epitopes, especially at the S14 area, that signals for cancer growth suppression and prevention. By using a simulated 3-dimentional structure and generated specific antibodies, WWOX epitopes were determined at amino acid #7 to 21 and #286 to 299. Synthetic WWOX7-21 peptide, or truncation to 5-amino acid WWOX7-11, significantly suppressed and prevented the growth and metastasis of melanoma and skin cancer cells in mice. Time-lapse microscopy revealed that WWOX7-21 peptide potently enhanced the explosion and death of 4T1 breast cancer stem cell spheres by ceritinib. This is due to rapid upregulation of proapoptotic pY33-WWOX, downregulation of prosurvival pERK, prompt increases in Ca2+ influx, and disruption of the IkBα/WWOX/ERK prosurvival signaling. In contrast, pS14-WWOX7-21 peptide dramatically increased cancer growth in vivo and protected cancer cells from ceritinib-mediated apoptosis in vitro, due to a prolonged ERK phosphorylation. Further, specific antibody against pS14-WWOX significantly enhanced the ceritinib-induced apoptosis. Together, the N-terminal epitopes WWOX7-21 and WWOX7-11 are potent in blocking cancer growth in vivo. WWOX7-21 and WWOX7-11 peptides and pS14-WWOX antibody are of therapeutic values in suppressing and preventing cancer growth in vivo.

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Therapeutic antibodies against cancer stem cells: a promising approach

Cited by 13 publications

References 115 publications

Ultrasound-Activated Piezoelectric Nanoparticles Inhibit Proliferation of Breast Cancer Cells

Ultrasound-Activated Piezoelectric Nanoparticles Inhibit Proliferation of Breast Cancer Cells

Initial Effects of the SB Natural Anticancer Drug on the Number of NK Cells, CD4+ and CD8+ T Lymphocytes in Human Peripheral Blood

WWOX Possesses N-Terminal Cell Surface-Exposed Epitopes WWOX7-21 and WWOX7-11 for Signaling Cancer Growth Suppression and Prevention In Vivo

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