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Pseudomonas Exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer
Fischer A, Wolf I, Fuchs H, Masilamani AP, Wolf P (2020) Pseudomonas Exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer. Toxins (Basel) 12(12):753. doi: 10.3390/toxins12120753
Summary: Refers to chimeric murine-human mAb cetuximab bound to Streptavidin-ZAP.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor.
Gick GG, Arora K, Sequeira JM, Nakayama Y, Lai SC, Quadros EV (2020) Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor. Exp Cell Res 396(1):112256. doi: 10.1016/j.yexcr.2020.112256
Summary: The increased and sustained expression of TCblR in proliferating cells has been used to target toxins preferentially to cancer cells and can be potentially used for targeted delivery of other anti-cancer drugs. In 2010 the authors published a paper which evaluated the potential of using immunotoxins to eliminate cancer cells expressing TCblR the authors performed a series of in vitro experiments using their monoclonal antibody plus Mab-ZAP in varying concentrations. The results indicated that this is a viable therapeutic model that causes minimal peripheral damage.
Related Products: Mab-ZAP (Cat. #IT-04)
The EphA2 and cancer connection: potential for immune-based interventions
London M, Gallo E (2020) The EphA2 and cancer connection: potential for immune-based interventions. Mol Biol Rep 47(10):8037-8048. doi: 10.1007/s11033-020-05767-y
Summary: The authors review the most current mAb-based therapies against EphA2-expressing cancers currently in pre-clinical and/or clinical stages. They reference Sakamoto et al. who performed in vitro testing of two different EphA2 mAbs mixed with Mab-ZAP to discover their therapeutic potential against melanoma.
Related Products: Mab-ZAP (Cat. #IT-04)
Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer
Zurlo G, Liu X, Takada M, Fan C, Simon JM, Ptacek TS, Rodriguez J, von Kriegsheim A, Liu J, Locasale JW, Robinson A, Zhang J, Holler JM, Kim B, Zikánová M, Bierau J, Xie L, Chen X, Li M, Perou CM, Zhang Q (2019) Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer. Nat Commun 10(1):5177. doi: 10.1038/s41467-019-13168-4 PMID: 31729379
Objective: To investigate the role of ADSL hydroxylation in controlling cMYC and triple negative breast cancer (TNBC) tumorigenesis.
Summary: ADSL regulates cMYC protein level through adenosine levels and leads to downstream metabolic changes and breast cancer cell proliferation. ADSL is essential for TNBC cell growth and invasiveness and contributes to TNBC breast tumorigenesis and metastasis in vivo.
Usage: Western blot
Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)
Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A.
Im E-J, Lee C-H, Moon P-G, Rangaswamy GG, Lee B, Lee JM, Lee J-C, Jee J-G, Bae J-S, Kwon T-K, Kang K-W, Jeong M-S, Lee J-E, Jung H-S, Ro H-J, Jun S, Kang W, Seo S-Y, Cho Y-E, Song B-J, Baek M-C (2019) Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A. Nature Commun 10(1):1387. doi: 10.1038/s41467-019-09387-4 PMID: 30918259
Objective: To identify a direct protein target of SFX in cancer cells.
Summary: Using data from the BindingDB, SEA identified four proteins as target candidates, which are: endothelin receptor type A, kynurenine 3-monooxygenase, carbonic anhydrase 13, and angiotensin II type 1a receptor.
Usage: Western blot (1:1000).
Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)
Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer
Tan HL, Yong C, Tan BZ, Fong WJ, Padmanabhan J, Chin A, Ding V, Lau A, Zheng L, Bi X, Yang Y, Choo A (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Sci Rep 8:11608. doi: 10.1038/s41598-018-30070-z
Objective: To identify and characterize an antibody raised using human embryonic stem cells with potential as a cancer therapeutic.
Summary: Antibody A19 not only binds to undifferentiated hESCs by flow cytometry, it also reacts with ovarian and breast cancer cell lines with low or no binding to normal cells.
Usage: in vitro – Number of viable cells treated showed a decrease in cell number (Hum-ZAP mixed with A19; Streptavidin-ZAP mixed with biotinylated A19). To determine if there were off-target effects, Hum-ZAP and chA19 were incubated with a non-binding cell line OVCAR10; no apparent cytotoxicity was observed. invivo – 5 x 106 SKOV3 cells were implanted s.c. in NUDE mice and Biotinylated A19-Streptavidin-ZAP (ADC), administered ip. The controls were free Saporin and naked A19. By the end of 10 weeks, mice administered with the ADC saw a 60% reduction in tumor size compared to control groups.
Related Products: Hum-ZAP (Cat. #IT-22), Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)
Role of GPCR (mu-opioid)-receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II).
Araldi D, Ferrari LF, Levine JD (2018) Role of GPCR (mu-opioid)-receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II). Pain 159(5):864-875. doi: 10.1097/j.pain.0000000000001155
Objective: To determine the the mechanisms mediating the induction of opioid-induced hyperalgesia and the prolongation of prostaglandinE2-induced hyperalgesia in type II hyperalgesic priming.
Summary: Understanding the mechanisms responsible for the induction of type II hyperalgesic priming, a form of neuroplasticity in the peripheral terminal of the primary afferent nociceptor, may provide useful information for the design of drugs with improved therapeutic profiles to treat neuroplasticity induced by chronic use of opioids.
Usage: SSP-SAP was prepared in saline (5 ng/mL), and 20 mL was injected intrathecally into rats, 14 days before nociceptive tests.
Related Products: SSP-SAP (Cat. #IT-11)
Synergistic cytotoxic effect on gastric cancer cells of an immunotoxin cocktail in which antibodies recognize different epitopes on CDH17
Kusano-Arai O, Iwanari H, Kudo S, Kikuchi C, Yui A, Akiba H, Matsusaka K, Kaneda A, Fukayama M, Tsumoto K, Hamakubo T (2018) Synergistic cytotoxic effect on gastric cancer cells of an immunotoxin cocktail in which antibodies recognize different epitopes on CDH17. Monoclon Antib Immunodiagn Immunother 37:1-11. doi: 10.1089/mab.2017.0043
Objective: To determine if an immunotoxin cocktail targeted to multiple epitopes has synergistic effects on low expression level cells, which would expand the applicable range of immunotoxin therapy for cancer.
Summary: The combination of immunotoxins with different mechanisms of action in an antibody cocktail will increase cytotoxic activities and decrease side effects.
Usage: The authors applied a monoclonal antibody (mAb) cocktail for one target protein with multiple epitopes. They generated anti-CDH17 mAbs recognizing different epitopes on CDH17 (Cadherin-17). CDH17 is expressed in gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer and has limited distribution in normal tissues. For preparation of 3 immunotoxins, Streptavidin-ZAP was mixed with biotinylated mAbs in equimolar concentrations for 30 minutes at room temperature. The study provides data to demonstrate that the cocktail of different epitope-recognizing immunotoxins has synergistic cytotoxic effects on CDH17-expressing cells.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448
Cua S, Tan HL, Fong WJ, Chin A, Lau A, Ding V, Song Z, Yang Y, Choo A (2018) Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448. Oncotarget 9:13206-13221. doi: 10.18632/oncotarget.24152
Objective: To develop mAbs to potentially target oncofetal antigens and be repurposed for antibody or antibody drug conjugate (ADC) therapy.
Summary: The novel IgG1, 2448, was shown to target a unique glycosylated surface epitope on ANXA2. As a possible therapeutic candidate for ovarian and breast cancer, 2448 demonstrated anti-tumor activity via two independent mechanisms of action.
Usage: Cells were seeded in 96-well plates at 1000 or 2000 cells/well. Primary antibody, 2448 or ch2448 (10 μg/mL) was pre-mixed with appropriate secondary saporin conjugate, Mab-ZAP or Hum-ZAP. The most significant decreases in cell viability (20% to 60%) were observed against the epithelial IGROV1 and MCF7 cell lines. ATS created a Custom ADC by direct conjugation of saporin to ch2448 (ch2448-SAP). As a control, an isotype chimeric IgG was also conjugated to saporin (IgG-SAP). Compared to using secondary saporin conjugates, ch2448-SAP induced and increase of 20–30% cytotoxicity.)
Related Products: Mab-ZAP (Cat. #IT-04), Hum-ZAP (Cat. #IT-22), Custom Conjugates
5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin
Lund K, Olsen CE, Wong JJW, Olsen PA, Solberg NT, Høgset A, Krauss S, Selbo PK (2017) 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185.. doi: 10.1186/s13046-017-0662-6
Objective: Investigate resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma.
Summary: Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and Anti-CD105-SAP was assessed using microscopy. MTS assay was used to investigate cytotoxic effects of photochemical internalization of Anti-CD105-SAP. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells using Anti-CD105-SAP in vitro. PCI-based targeting of CD105 may represent a potent anti-cancer strategy and should be further evaluated in preclinical models.
Usage: Cells were seeded (3000/well) in 96-well plates and allowed to attach overnight. The cells were incubated with the Anti-CD105-saporin (2.4 nM) or Saporin as a control (6.48 nM; Saporin was added in a molecular ratio of 2.7:1 to the immunotoxin) giving an equal ratio of Saporin to immunotoxin), with or without the photosensitizer TPCS2a (0.35 μg/ml) for 18 h.
Related Products: Anti-CD105-SAP (Cat. #IT-80)