Anti-IGF1R Recombinant Antibody (Dalotuzumab) (CAT#: TAB-736)

Recombinant humanized (from mouse) antibody expressed in CHO binding to IGF1R. Dalotuzumab is a humanized monoclonal antibody designed for the treatment of cancers.


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WB

Figure 1 Cotreatment with dalotuzumab and ridaforolimus enhances antitumor activity in IGF1Rexpressing tumors.

Figure 1 Cotreatment with dalotuzumab and ridaforolimus enhances antitumor activity in IGF1Rexpressing tumors.

A, Western blot analysis of PI3K pathway components in cancer cells treated with dalotuzumab, ridaforolimus, or the combination. In IGF1R-expressing cancer cell lines (H2122), combination treatment suppresses the activation of AKT demonstrated by decreased phosphorylation of AKT and downstream targets FOXO3A and PRAS40. B, combination therapy with ridaforolimus and dalotuzumab results in increased cell death in anchorage-independent growth inhibition assays in IGF1R-expressing cells (H2122). No such combination benefit was observed in cancer cells expressing low levels of IGF1R (H1703). C, In vivo, combination therapy with ridaforolimus and dalotuzumab significantly inhibits growth over monotherapies. Tumor growth of primary human tumor-derived lung adenocarcinoma xenograft model LXFA629 in control (vehicle) or experimental agenttreated mice (n =10/group) were plotted. Combination therapy with ridaforolimus and dalotuzumab significantly enhanced tumor growth inhibition compared to vehicle-treated (P < 0.0001) or single-agent treated groups (P < 0.05).

Di Cosimo, S., Sathyanarayanan, S., Bendell, J. C., Cervantes, A., Stein, M. N., Braña, I.,... & Jha, S. (2015). Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial. Clinical Cancer Research, 21(1), 49-59.

Activ

Figure 2 Combination therapy with mTOR and IGF1R inhibitors block feedback activation of AKT.

Figure 2 Combination therapy with mTOR and IGF1R inhibitors block feedback activation of AKT.

A, diversity in feedback activation of AKT by ridaforolimus was observed in a panel of breast cancer cell lines. B, cell lines exhibiting feedback activation of AKT following ridaforolimus treatment showed sensitivity to anti-IGF1R therapy. C, knockdown of IGF1R and its signaling pathway components blocked feedback activation of AKT. A lentiviral shRNA screen identified mTOR as an enhancer of the activity of dalotuzumab in tumor cell lines, and AKT activation by mTOR was confirmed to be mediated via the IGF1R signaling pathway. D, representative results from a shRNA screen targeting various PI3K and MAPK kinases in HT-29 CRC cells. mTOR, mammalian target of rapamycin; IGF1R, insulin-like growth factor 1 receptor; shRNA, short hairpin RNA; PI3K, phosphatidylinositol 3-kinase; CRC, colorectal cancer; PTEN, phosphatase and tensin homolog.

Di Cosimo, S., Sathyanarayanan, S., Bendell, J. C., Cervantes, A., Stein, M. N., Braña, I.,... & Jha, S. (2015). Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial. Clinical Cancer Research, 21(1), 49-59.

Inhib

Figure 3 IGF-1R inhibition (MK-0646) does not enhance hormonal therapy (letrozole or tamoxifen) in MCF-7/AC-1 xenografts.

Figure 3 IGF-1R inhibition (MK-0646) does not enhance hormonal therapy (letrozole or tamoxifen) in MCF-7/AC-1 xenografts.

Ovariectomized female nu/nu mice between the ages of 7–8 weeks old were inoculated with MCF-7/AC-1 tumor cells in each flank and immediately supplemented with androstenedione (100 μg/day). Once bilateral flank tumors (both left and right) reached the appropriate size (250–300 mm3), mice were randomized (n ≥ 8 mice/cohort) and the appropriate treatments initiated (control, MK-0646, letrozole (LET), LET + MK-0646, tamoxifen (TAM), TAM + MK-0646) for a total of 28 days. Tumor volumes were measured twice weekly and depicted as percent change relative to day 0. Error bars represent SEM and results are representative of three independent experiments.

Becker, M. A., Hou, X., Tienchaianada, P., Haines, B. B., Harrington, S. C., Weroha, S. J.,... & Haluska, P. (2016). Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC cancer, 16(1), 814.

WB

Figure 4 MK-0646 increases Insulin Receptor A Isoform expression in MCF-7/AC-1 xenografts.MCF-7/AC-1 xenograft tumors were harvested and immediately flash frozen following 28 days of treatment.

Figure 4 MK-0646 increases Insulin Receptor A Isoform expression in MCF-7/AC-1 xenografts.MCF-7/AC-1 xenograft tumors were harvested and immediately flash frozen following 28 days of treatment.

RNA and protein were extracted for Insulin Receptor and IGF-1R quantification by qPCR (a) and western blot analysis (b) as described in the methods. a Absolute IGF1R (Top) and IRA/B isoform (Bottom) copy number normalized to RPL19 housekeeper. b Protein from pooled group replicates isolated at indicated time points were subject to western blotting with indicated antibodies, as described in Materials and Methods section. Error bars represent SEM. *, P < 0.05; **, P < 0.01; ***, P <0.001; **** P < 0.0001.

Becker, M. A., Hou, X., Tienchaianada, P., Haines, B. B., Harrington, S. C., Weroha, S. J.,... & Haluska, P. (2016). Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC cancer, 16(1), 814.

Inhib

Figure 5 Persistent mTOR signaling in response to IGF-1R inhibition is overcome by MK-8669.

Figure 5 Persistent mTOR signaling in response to IGF-1R inhibition is overcome by MK-8669.

Western Blot analysis of MCF-7/AC-1 (a) and MCF-7/AC-1/IGF-2 (b) cells treated with one or more of the following agents for 24 h at the indicated dose(s): LET (1uM), MK-0646 (1.25, 2.5, 5 ng/uL) and/or MK-8669 (100, 500, 1000 nM). IGF-1 was added for 10 min prior to harvest for the indicated samples.

Becker, M. A., Hou, X., Tienchaianada, P., Haines, B. B., Harrington, S. C., Weroha, S. J.,... & Haluska, P. (2016). Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC cancer, 16(1), 814.

Activ

Figure 6 In vivo activity of LET +/− MK-8669 +/− MK-0646 in MCF-7/AC-1 xenografts.

Figure 6 In vivo activity of LET +/− MK-8669 +/− MK-0646 in MCF-7/AC-1 xenografts.

a As previously described, ovariectomized female nu/nu mice between the ages of 7–8 weeks old were inoculated with MCF-7/AC-1 tumor cells in each flank and immediately supplemented with androstenedione (100 μg/day). Once bilateral flank tumors (both left and right) reached the appropriate size (250–300 mm3), mice were randomized (n ≥ 9 mice/cohort) and the appropriate treatments initiated (Control, LET, MK-8669, MK-0646, MK-8669 + MK-0646, LET + MK-0646, LET + MK-8669 or LET + MK-0646 + MK-8669) for a total of 28 days. Tumor volumes were measured weekly and depicted as percent change relative to day 0. Error bars represent SEM and results are representative of two independent experiments. b Tumors from treatment groups were collected 28 days post treatment initiation, immediately snap frozen and lysates pooled (n ≥ 3 samples/treatment cohort) for Western Blot analysis.

Becker, M. A., Hou, X., Tienchaianada, P., Haines, B. B., Harrington, S. C., Weroha, S. J.,... & Haluska, P. (2016). Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer. BMC cancer, 16(1), 814.


Specifications

  • Immunogen
  • The details of the immunogen for this antibody are not available.
  • Host Species
  • Mouse
  • Derivation
  • Humanized (from mouse)
  • Type
  • IgG1 - kappa
  • Species Reactivity
  • Human
  • Applications
  • FC, IP, ELISA, Neut, FuncS, IF, ICC, WB, Activ, Inhib
  • CAS
  • 1005389-60-5
  • Generic Name
  • dalotuzumab
  • UNII
  • 6YI1L648RH
  • MW
  • 146.4 kDa
  • Related Disease
  • Solid tumors

Product Property

  • Purity
  • Purity >95% by SDS-PAGE.
  • Storage
  • Store at -20°C for long-term storage. Store at 2-8°C for up to one month. Avoid freeze/thaw cycles.

Applications

  • Application Notes
  • The IGF1R antibody has been reported in applications of FC, IP, ELISA, Neut, FuncS, IF, ICC, WB, Activ, Inhib.

Target

  • Alternative Names
  • dalotuzumab;1005389-60-5;MK-0646;MK0646;h7C10;IGF1R;insulin-like growth factor 1 receptor;CD221;IGFIR;IGFR;JTK13;MGC18216;IGF-I receptor;soluble IGF1R variant 1;soluble IGF1R variant 2;insulin-like growth factor I receptor;MGC142170;MGC142172;

Related Resources

  • Biosimilar Overview
  • Related Signaling Pathways
  • Related Diseases
Please refer to Dalotuzumab Overview to learn more about the mechanism of action, clinical projects, and approved drugs of Dalotuzumab.

Product Notes

This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:

• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production

See more details about Hi-Affi™ recombinant antibody benefits.

Downloads

Download resources about recombinant antibody development and antibody engineering to boost your research.

See other products for "Dalotuzumab"

Afuco™ Anti-IGF1R ADCC Recombinant Antibody (Dalotuzumab), ADCC Enhanced
This product is an ADCC enhanced antibody produced by our Afuco™ platform. Recombinant humanized (from mouse) antibody expressed in CHO binding to IGF1R. Dalotuzumab is a humanized monoclonal antibody designed for the treatment of cancers.

See other products for "IGF1R"

Immunotoxin

CAT Product Name Application Type
AGTO-L024E IGF1-PE immunotoxin Cytotoxicity assay, Functional assay
AGTO-L024D IGF1-DT immunotoxin Cytotoxicity assay, Functional assay

Chimeric Antibody

CAT Product Name Application Type
TAB-084ZJ Human Anti-IGF1R Recombinant Antibody (TAB-084ZJ) WB, Inhib, ELISA, FC Chimeric (mouse/human) IgG
TAB-085ZJ Anti-Human IGF-1R Recombinant Antibody (6E11c) ELISA, FC, IHC, Inhib Chimeric antibody (mouse/human)
TAB-086ZJ Human Anti-IGF1R Recombinant Antibody (TAB-086ZJ) ELISA, FC, Inhib, IP Chimeric (mouse/human) IgG1
TAB-087ZJ Anti-Human IGF-1R Recombinant Antibody (ch7C2) ELISA Chimeric antibody (mouse/human)
TAB-093ZJ Anti-Human IGF-1R Recombinant Antibody (ch9E11) ELISA Chimeric antibody (mouse/human)

Chicken IgY Antibody

CAT Product Name Application Type
BRD-0103MZ Chicken Anti-CD221 Polyclonal IgY WB Chicken antibody

Neutralizing Antibody

Blocking Antibody

CAT Product Name Application Type
NEUT-1077CQ Mouse Anti-IGF1R Recombinant Antibody (clone 1H7) FC, Block, IHC, IP, WB Mouse IgG1, κ
NEUT-1078CQ Mouse Anti-IGF1R Recombinant Antibody (clone 24-60) Inhib, ICC, IF, IP, WB Mouse IgG2a, κ
NEUT-1079CQ Mouse Anti-IGF1R Recombinant Antibody (clone 17-69) Inhib, IP Mouse IgG1
NEUT-1080CQ Mouse Anti-IGF1R Recombinant Antibody (clone 24-57) Inhib, IP Mouse IgG1, κ

Recombinant Antibody

ADCC Enhanced Antibody

CAT Product Name Application Type
AFC-TAB-199 Afuco™ Anti-IGF1R Recombinant Antibody (AFC-TAB-199), ADCC Enhanced FC, IP, ELISA, Neut, FuncS, IF Human IgG1, κ
AFC-TAB-209 Afuco™ Anti-IGF1R ADCC Recombinant Antibody (Robatumumab), ADCC Enhanced FuncS, IF, Neut, ELISA, FC, IP ADCC enhanced antibody
AFC-TAB-736 Afuco™ Anti-IGF1R ADCC Recombinant Antibody (Dalotuzumab), ADCC Enhanced FC, IP, ELISA, Neut, FuncS, IF ADCC enhanced antibody
AFC-TAB-078 Afuco™ Anti-IGF1R ADCC Recombinant Antibody (Cixutumumab), ADCC Enhanced IF, IP, Neut, FuncS, ELISA, FC ADCC enhanced antibody
AFC-TAB-232 Afuco™ Anti-IGF1R ADCC Recombinant Antibody (Figitumumab), ADCC Enhanced IF, IP, Neut, FuncS, ELISA ADCC enhanced antibody

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For Research Use Only. Not For Clinical Use.

For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.

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