Anti-GM2 ADCC Enhanced Antibody (BIW-8962) is an ADCC enhanced antibody produced by our Afuco™ platform. BIW-8962 is a humanized anti-ganglioside GM2 (GM2) monoclonal antibody, exhibited a potent ADCC and less potent CDC activity. Currently BIW-8962 is being investigated in a Phase 1 study in patients with multiple myeloma.
Figure 1 To determine the mode of action of these anti-GM2 antibodies, we histologically analyzed liver metastases treated with PBS (control) or anti-GM2 antibodies.
Histological examination of metastatic lesions treated with anti-ganglioside GM2 antibodies. SBC-3 (1 × 10⁶) small-cell lung cancer cells were inoculated i.v. into natural killer cell-depleted SCID mice. The mice were injected with PBS, control IgG, KM966, BIW-8962, or KM8927, on days 7, 14, 21, 28, and 35 and killed on day 42. Metastatic liver lesions were harvested and stained with H&E, and for Ki-67, an indicator of cell proliferation, TUNEL, an indicator of cell apoptosis, and GM2 expression. (A) Microscopic appearance of lesions. (B) Quantification of the percentage of Ki-67-positive cancer cells and (C) the number of TUNEL-positive apoptotic cells. Data shown are the mean ± SD of five independent areas. Results shown are representative of at least two independent experiments. HPF, high power field. *P < 0.05 compared with control.
Yamada,T.,Bando,H.,Takeuchi,S.,Kita,K.,Li,Q.,Wang,W.,& Yano, S.(2011).Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by GM2-expressing small-cell lung cancer cells. Cancer science, 102(12), 2157-2163.
Figure 2 treatment with these mAbs dramatically prolonged survival of the mice compared with control.
Effect of anti-ganglioside GM2 antibodies on survival of SBC-3-bearing mice. SBC-3 (1 × 10⁶) small-cell lung cancer cells were inoculated i.v. into natural killer cell-depleted SCID mice. The mice (10 per group) were treated with PBS, control IgG, KM966, BIW-8962, or KM8927, once a week starting on day 7. Results shown are representative of two independent experiments. *P < 0.001 compared with control.
Yamada,T.,Bando,H.,Takeuchi,S.,Kita,K.,Li,Q.,Wang,W.,& Yano, S.(2011).Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by GM2-expressing small-cell lung cancer cells. Cancer science, 102(12), 2157-2163.
Figure 3 GM2 expression in MPM cell lines.
Expression levels of ganglioside GM2 were evaluated in malignant pleural mesothelioma cell lines. Cells were detached and incubated with BIW-8962 or anti-dinitrophenol (DNP) antibodies on ice for 30 min. Bound Abs were detected with FITC-conjugated goat anti-human IgG Abs. The fluorescence intensity of the stained cells was measured using flow cytometry, and the mean fluorescence intensity was calculated. The open red histograms represent BIW-8962-stained samples and the filled blue histograms represent anti-DNP antibody-stained samples. The relative fluorescent intensity (RFI) versus anti-DNP is indicated.
Li,Q.,Wang,W.,Machino,Y.,Yamada T.,Kita,K.,Oshima,M.,& Iida, S. (2015). Therapeutic activity of glycoengineered anti-GM 2 antibodies against malignant pleural mesothelioma. Cancer science, 106(1), 102-107.
Figure 4 Antibody-dependent cellular cytotoxicity activity against MPM cell line.
Anti-GM2 antibody BIW-8962 exerted antibody-dependent cellular cytotoxicity activity against MSTO-211H malignant pleural mesothelioma cells. Human peripheral blood mononuclear cells were purified from healthy donors and used as effector cells. MSTO-211H cells (target cells) were incubated with effector cells (effector/target = 25/1, 50/1, and 100/1) and antibodies (BIW-8962 or anti-dinitrophenol antibodies) at 37°C for 4 h. The released lactate dehydrogenase activity was measured and the % cytotoxicity was calculated. The experiments were carried out in triplicate, and the values are expressed as the mean of the values for four donors ± SD. *P < 0.01, **P < 0.001 BIW-8962 treatment versus anti-dinitrophenol antibody treatment.
Li,Q.,Wang,W.,Machino,Y.,Yamada T.,Kita,K.,Oshima,M.,& Iida, S. (2015). Therapeutic activity of glycoengineered anti-GM 2 antibodies against malignant pleural mesothelioma. Cancer science, 106(1), 102-107.
Figure 5 In vivo therapeutic activity of BIW-8962 in orthotropic mouse model.
Anti-GM2 antibody BIW-8962 showed therapeutic activity in an MSTO-211H orthotropic mouse model. MSTO-211H malignant pleural mesothelioma cells were inoculated into the thoracic cavity in SCID mice, and the animals were treated with BIW-8962 and/or human peripheral blood mononuclear cells (MNC). The mice were then i.v. administered BIW-8962 and/or MNC on days 7 and 14. At 3 weeks after tumor cell inoculation, the mice were sacrificed and their tumor weights were measured. The bars represent the mean of the group data. *P < 0.05 and **P < 0.01 between each treatment and the control groups.
Li,Q.,Wang,W.,Machino,Y.,Yamada T.,Kita,K.,Oshima,M.,& Iida, S. (2015). Therapeutic activity of glycoengineered anti-GM 2 antibodies against malignant pleural mesothelioma. Cancer science, 106(1), 102-107.
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• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production
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CAT | Product Name | Application | Type |
---|---|---|---|
MOB-406 | Recombinant Anti-GM2 Antibody | ELISA, WB, IF, FuncS | IgG |
MHH-406 | Recombinant Human Anti-GM2 Antibody | WB, Neut, FuncS | IgG |
HPAB-S0039-YC | Human Anti-GM2 Recombinant Antibody (clone KM8966) | ELISA, ADCC | Human IgG |
HPAB-S0040-YC | Human Anti-GM2 Recombinant Antibody (clone KM8967) | ELISA, ADCC | Human IgG |
FAMAB-0054WJ | Human Anti-GM2 Recombinant Antibody (clone L55-81) | WB, ELISA, Cyt, IHC | Human IgM |
CAT | Product Name | Application | Type |
---|---|---|---|
MOB-406-F(E) | Recombinant Anti-GM2 Antibody Fab Fragment | IP, FuncS | Fab |
MHH-406-F(E) | Recombinant Human Anti-GM2 Antibody Fab Fragment | ELISA, IP, FuncS | Fab |
HPAB-S0039-YC-F(E) | Human Anti-GM2 Recombinant Antibody (clone KM8966); Fab Fragment | ELISA, ADCC | Human Fab |
HPAB-S0040-YC-F(E) | Human Anti-GM2 Recombinant Antibody (clone KM8967); Fab Fragment | ELISA, ADCC | Human Fab |
MOB-102YJL-F(E) | Mouse Anti-GM2 Recombinant Antibody (clone KM796); Fab Fragment | ELISA, ADCC, CDC, FuncS | Mouse Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
MOB-406-S(P) | Recombinant Anti-GM2 Antibody scFv Fragment | IF, FC, Biosensors, FuncS | scFv |
MHH-406-S(P) | Recombinant Human Anti-GM2 Antibody scFv Fragment | WB, IF, FuncS | scFv |
HPAB-S0040-YC-S(P) | Human Anti-GM2 Recombinant Antibody (clone KM8967); scFv Fragment | ELISA, ADCC | Human scFv |
FAMAB-0054WJ-S(P) | Human Anti-GM2 Recombinant Antibody (clone L55-81); scFv Fragment | WB | Human scFv |
MOB-102YJL-S(P) | Mouse Anti-GM2 Recombinant Antibody (clone KM796); scFv Fragment | ELISA, ADCC, CDC, FuncS | Mouse scFv |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-320CL | Anti-Human GM2 Recombinant Antibody (BIW-8962) | FC, FuncS, IF | Antibody |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-169CT | Anti-Human GM2 (Monosialo-GM2) Recombinant Antibody (DMF10.62.3) | ELISA, FC, IHC | |
TAB-170CT | Anti-Human GM2 (Monosialo-GM2) Recombinant Antibody (DMF10.167.4) | IHC, FC, WB, Inhib, IF, ELISA | |
TAB-169CT-S(P) | Anti-Human GM2 (Monosialo-GM2) Recombinant Antibody scFv Fragment (DMF10.62.3) | ELISA, FC, IHC | |
TAB-170CT-S(P) | Anti-Human GM2 (Monosialo-GM2) Recombinant Antibody scFv Fragment (DMF10.167.4) | ELISA, FC, IHC | |
TAB-169CT-F(E) | Anti-Human GM2 (Monosialo-GM2) Recombinant Antibody Fab Fragment (DMF10.62.3) | ELISA, FC, IHC |
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