Anti-ICAM1 ADCC Enhanced Antibody (BI-505) is an ADCC enhanced antibody produced by our Afuco™ platform. BI-505 is a fully human high-affinity IgG1 antibody, which was isolated from a highly diverse human phage-antibody library based on its functional ability to induce programmed cell death of tumor cells. BI-505 binds to intercellular adhesion molecule-1 (ICAM-1), suggesting a previously unrecognized role for this receptor as a therapeutic target in cancer.
Figure 1 Observed BI-505 serum concentration versus time curves (mean ± SD) in dose groups from 0.9 mg/kg and higher.
A. Pharmacokinetics after first dose. B. Pharmacokinetics after multiple doses. LLOQ indicates lower limit of quantification; and arrow indicate BI-505 infusions.
Hansson, M., Gimsing, P., Badros, A., Niskanen, T. M., Nahi, H., Offner, F., ... & Sundberg, A. (2015). A phase I dose-escalation study of antibody BI-505 in relapsed/refractory multiple myeloma. Clinical Cancer Research, 21(12), 2730-2736.
Figure 2 BI-505 Has Significant In Vivo Antitumor Activity against CD20-Expressing Tumors Compared with Rituximab
(A–H) Mean tumor volumes (A, C, E, and G) and survival (B, D, F, and H) of mice xenografted with CD20-expressing ARH-77 (A–D) or Daudi (E–H) cells and treated with BI-505 (bright red line = 20 mg/kg BI-505; maroon line = 2 mg/kg BI-505; and orange line = 0.2 mg/kg BI-505), rituximab (20 mg/kg, blue line), or isotype control (20 mg/kg, black line) antibodies in prophylactic (A, B, E, and F) or established (C, D, G, and H) tumor models. There were eight to ten animals per treatment/dose group. Tumor cells were injected day 0, and antibody treatment started as indicated in the graphs (black arrow). *p < 0.05, **p < 0.01, and ***p < 0.001. Error bars show ± SD. (I and J) FACS analysis of BI-505 and rituximab epitopes on the surface of ARH-77 (I) and Daudi (J) tumor cells. Antibodies were used at binding saturating concentrations.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 3 BI-505 Dose-Dependent Antitumor Activity Correlates with ICAM-1 Receptor Occupancy on Tumor Cell Surfaces
(A and B) Mean tumor volumes (A) and mean survival (B) of mice treated with different doses of BI-505 in the ARH-77 tumor model. Error bars show ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001. (C–E) BI-505 concentration-dependent in vivo antitumor activity (C), in vitro antitumor (tumor PCD) activity (D), and receptor occupancy of tumor cell-expressed ICAM-1 (E). (F) A combined plot of (C)–(E). There were eight to ten animals per treatment group.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 4 The BI-505 Epitope Is Highly Expressed on the Surface of Primary MM Plasma Cells.
FACS analysis of BI-505 epitope expression on the cell surface of patients' MM cells (red bars) versus normal B cells (yellow bars). Numbers on top of bars indicate fold increase of the BI-505 epitope on surface of MM cells compared to normal B cells.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 5 BI-505 Has Broad and ICAM-1- Dependent Anti-MM Activity In Vivo.
(A) Tumor volume (mean ± SD) of NCI-H929 (ICAM-1+), EJM (ICAM-1+), RPMI-8226 (ICAM-1+), and OPM-2 (ICAM-1) MM models after treatment with 2 mg/kg BI-505 (filled circles) or control (open circles) antibody. (B) Relative tumor volumes following treatment with 2 mg/kg BI-505 (filled bars) or control (open bars) antibody in NCI-H929, EJM, RPMI-8226, and OPM-2 MM models. Graph shows tumor volumes (mean ± SD) relative to the mean tumor volume of control IgG-treated animals. There were eight animals per treatment group.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 6 BI-505 Confers Enhanced Survival Compared to Currently Used Treatments in Disseminated Experimental Models of Advanced MM.
(A) Animal survival in advanced disseminated RPMI-8226 myeloma model following treatment with control antibody, lenalidomide, bortezomib, dexamethasone (DXH), melphalan, or BI-505. ***p < 0.001. (B) Human immunoglobulin G (hIgG) (mean ± SD) in SCID-hu mice after myeloma cell inoculation and drug treatment. Graph shows pooled data from two independent experiments, each with MM cells obtained from two different patient donors (n = 4). The percentage of hIgG levels compared to start of treatment (arrow) was monitored. ***p < 0.001. (C) Myeloma tumor burden in implanted bones harvested from drug-treated mice. Pictures show representative images of tumor burden as assessed by immunohistochemistry following staining for human CD138-expressing cells. Arrows indicate human CD138-positive myeloma cell regions. Scale bar = 50 mm. (D) X-radiographic quantification of bone mineral density. Radiographs of implanted human bones receiving drug or control treatment were harvested from mice at end of experimentation (10 weeks postmyeloma cell injection and following 6 weeks of drug treatment). Upper panel shows representative radiographs of bones from healthy mice, control IgG-treated mice, BI-505-treated mice, or bortezomib-treated mice (left to right). Lower panel shows mean ± SD bone mineral density of mice receiving treatment as indicated. *p < 0.05. (E and F) Representative images of trap staining (purple stain) for detection of osteoclasts (E) or hematoxylin and eosin staining for detection of infiltrated nucleated cells (F) performed on healthy and MM cell-injected bones harvested from SCIDhu mice treated as indicated at end of experimentation. Scale bar = 100 mm.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 7 BI-505 Confers Fc-FcgR-Dependent Antitumor Activity through Macrophages.
(A) Mean tumor volume of SCID mice bearing established ARH-77 tumors and treated with isotype control antibody or BI-505 IgG1, BI-505 IgG4, or BI-505 IgG1 N297Q (Fc-variant) antibodies. *p < 0.05, **p < 0.01. (B) BiaCore analysis of BI-505 Fc-variant antibodies binding to mouse FcgRIV. (C) BiaCore analysis of BI-505 Fc-variant antibodies binding to human FcgRIIIa. (D) Immunohistochemical quantitation of F4/80+ macrophages (top panel) or NK cells (lower panel) in tumor tissue of animals bearing established ARH-77 tumors treated with control antibody or BI-505. Graphs show mean F4/80+ and NK-cellpositive tumor areas, respectively. Bar = 40 mm. *p < 0.05, ***p < 0.001. (E) Tumor growth in macrophage or NK-celldepleted SCID mice bearing established RPMI- 8226 myeloma tumors treated with BI-505 or control antibody. ***p < 0.001. (F) Animal survival following BI-505 or control antibody treatment in a disseminated NK-celldeficient NOD/Shi-scid/IL-2Rg/mouse model comprising i.v. grafted U266 myeloma cells. ***p < 0.001. (G) Tumor growth in BI-505 or control antibodytreated NK-cell-deficient NOD/Shi-scid/IL-2Rg/mice transplanted with RPMI-8226 myeloma cells. ***p < 0.001. (H) Macrophage ADCP of RPMI-8226 and OPM-2 myeloma cells. n = 4, ***p < 0.001. (I) Macrophage-mediated ADCP of primary multiple myeloma cells. n = 2, ***p < 0.001. (J) Macrophage ADCP of ICAM-1+ EJM myeloma cells. n = 2, ***p < 0.001.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
Figure 8 BI-505 Does Not Induce Apoptosis, ADCC, CDC, T Cell Proliferation, or Cytokine Release in Resting or Stimulated Normal Cells Expressing ICAM-1.
(A) Apoptosis in peripheral blood B cells. Graph shows percent live (nonapoptotic) B cells following no treatment or treatment with isotype control IgG, anti-HLADR (positive control IgG), or BI-505 (0, 1.5, 6, or 24 mg/ml). Values were normalized to untreated cells, where percent living cells was set to 100. (B) ADCC of peripheral blood B cells. Graph shows specific lysis of target peripheral blood B cells following treatment with BI-505 or anti-HLA-DR IgG1 (positive control). Values were normalized to treatment with isotype control IgG, where specific lysis was set to 0%. (C) CDC of peripheral blood B cells and Daudi Burkitt's lymphoma cells. Cells were incubated with BI-505, rituximab, or isotype control IgG and analyzed for CDC. (D) Antibody-induced PBMC cytokine release. PBMC cytokine release was measured by ELISA of cell culture supernatants for IL-1b, IL-2, IL-6, IL-8, IFN-g, and TNF-a following incubation of cells in plates coated with hypercrosslinked (air-dried ''A'' or wet-coated ''W'') BI-505, isotype control, or positive-control Okt-3 antibody. (E) Antibody-induced cytokine release in lipopolysaccharide (LPS)-primed PBMCs. PBMCs were incubated with titrated LPS, and concentrations yielding submaximal cellular release of IL-1b (100 pg/ml), IL-6 (10 pg/ml), IL-8 (10 pg/ml), and TNF-a (10 pg/ml) were determined (arrows, left panel) and used in subsequent experiments assessing antibody (BI-505 or control IgG) effects on cytokine release from LPS-primed PBMCs (right panel). Treatment with 100 ng/ml LPS served as positive control for robust cytokine release. (F) Antibody-induced T cell proliferation. CFSE-labeled T cells were incubated with BI-505, isotype control IgG, or anti-CD3 (okt-3) IgG hyperimmobilized to cell culture plates by air-drying ''A'' or wet-coating ''W.'' Cells were cultured for 6 days, and T cell proliferation was monitored by flow cytometry as decreased CFSE signals. (G) Antibody-induced endothelial cell apoptosis. HUVEC or HMVEC endothelial cells were incubated with paclitaxel (positive control), BI-505, or isotype control IgG in the presence or absence of crosslinking mAb. Apoptosis was measured by flow cytometry following staining of cells with annexin V-AF488. **p < 0.01, ***p < 0.001. Error bars show ± SD.
Veitonmäki, N., Hansson, M., Zhan, F., Sundberg, A., Löfstedt, T., Ljungars, A., ... & Danielsson, L. (2013). A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell, 23(4), 502-515.
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CAT | Product Name | Application | Type |
---|---|---|---|
NAB-1937-VHH | Recombinant Anti-human ICAM1 VHH Single Domain Antibody | FA, FC, ICC, ELISA | Llama VHH |
TAB-126CT | Llama Anti-ICAM1 Recombinant Antibody (TAB-126CT) | ELISA, IF | Llama VHH |
HPAB-0349-YC-VHH | Recombinant Llama Anti-ICAM1 Single Domain Antibody (34-1) | ELISA | Llama VHH |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-241 | Anti-Human ICAM-1 Recombinant Antibody Fab Fragment (Enlimomab Pegol) | WB, IF, IP, Neut, FuncS, ELISA, FC | Fab' - G2a |
TAB-H26 | Anti-Human ICAM1 Recombinant Antibody (Enlimomab) | Neut, ELISA, IF, IP, FuncS, FC, WB | IgG2a |
TAB-124CT | Anti-Human ICAM-1 Recombinant Antibody (m1A6) | ELISA | |
TAB-124CT-S(P) | Anti-Human ICAM-1 Recombinant Antibody scFv Fragment (m1A6) | ELISA | |
TAB-124CT-F(E) | Anti-Human ICAM-1 Recombinant Antibody Fab Fragment (m1A6) | ELISA |
CAT | Product Name | Application | Type |
---|---|---|---|
AGTO-L023R | anti-ICAM1 immunotoxin UV3 (IgG)-RTA | Cytotoxicity assay, Functional assay |
CAT | Product Name | Application | Type |
---|---|---|---|
PFBZ-079 | Mouse Anti-ICAM1 Recombinant Antibody (clone CA7); Fab Fragment | FC | Mouse Fab |
HPAB-0859-CN-F(E) | Human Anti-ICAM1 Recombinant Antibody (clone BI-AB); Fab Fragment | ELISA, FC, Neut | Human Fab |
HPAB-662-FY-F(E) | Human Anti-ICAM1 Recombinant Antibody (clone ICM10088); Fab Fragment | Inhib | Human Fab |
HPAB-1728-FY-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone LAC1555); Fab Fragment | ELISA | Human Fab |
HPAB-1729-FY-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone LAC3040); Fab Fragment | ELISA | Human Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-121CT | Anti-Human ICAM-1 Recombinant Antibody (MD-2) | ELISA, FC | Human antibody |
TAB-125CT | Anti-Human ICAM-1 Recombinant Antibody (ICM 10064) | Inhibit, ELISA, WB | Human antibody |
TAB-121CT-S(P) | Anti-Human ICAM-1 Recombinant Antibody scFv Fragment (MD-2) | ELISA, FC | Human antibody |
TAB-122CT-S(P) | Anti-Human ICAM-1 Recombinant Antibody scFv Fragment (R6-5-D6) | ELISA, FC | Human antibody |
TAB-125CT-F(E) | Anti-Human ICAM-1 Recombinant Antibody Fab Fragment (ICM 10064) | Inhibit, ELISA, WB | Human antibody |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-123CT | Anti-Human ICAM-1 Recombinant Antibody (h1A6) | ELISA | Humanized antibody |
TAB-123CT-S(P) | Anti-Human ICAM-1 Recombinant Antibody scFv Fragment (h1A6) | ELISA | Humanized antibody |
TAB-123CT-F(E) | Anti-Human ICAM-1 Recombinant Antibody Fab Fragment (h1A6) | ELISA | Humanized antibody |
CAT | Product Name | Application | Type |
---|---|---|---|
Gly-104LC | Recombinant Anti-Human ICAM1 Antibody (Fc glycosylation) | ELISA | Mouse antibody |
CAT | Product Name | Application | Type |
---|---|---|---|
NEUT-923CQ | Mouse Anti-ICAM1 Recombinant Antibody (clone CBL236) | Neut, IF, FC, WB, IHC | Mouse IgG1 |
NEUT-925CQ | Mouse Anti-ICAM1 Recombinant Antibody (clone HA58) | FC, FuncS, IHC, Neut, WB | Mouse IgG1, κ |
NEUT-926CQ | Mouse Anti-ICAM1 Recombinant Antibody (VMC182) | FC, IF, IHC, ICC, Neut | Mouse IgG2b |
NEUT-927CQ | Mouse Anti-ICAM1 Recombinant Antibody (clone RR1/1) | FC, IF, IHC, Neut, WB, ELISA | Mouse IgG1 |
NEUT-933CQ | Mouse Anti-Icam1 Recombinant Antibody (clone 1A29) | WB, IP, ICC, IF, IHC-P, Neut, FC | Mouse IgG1 |
CAT | Product Name | Application | Type |
---|---|---|---|
NEUT-924CQ | Mouse Anti-ICAM1 Recombinant Antibody (clone HCD54) | FC, IF, Block | Mouse IgG1, κ |
NEUT-928CQ | Mouse Anti-ICAM1 Recombinant Antibody (VMC183) | Block, FC, IHC, IP | Mouse IgG1 |
NEUT-929CQ | Mouse Anti-ICAM1 Recombinant Antibody (clone BBIG-I1(11C81)) | Block, WB, IP, ICC | Mouse IgG1 |
CAT | Product Name | Application | Type |
---|---|---|---|
MOR-1723 | Rabbit Anti-ICAM1 Recombinant Antibody (clone DS1723AB), Biotin | IHC-Fr, IP, WB, ELISA | Rabbit IgG |
MOR-1724 | Rabbit Anti-Icam1 Recombinant Antibody (clone DS1724AB) | ELISA | Rabbit IgG |
MOR-4598 | Rabbit Anti-ICAM1 Recombinant Antibody (clone TH111DS) | WB, FC | Rabbit IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
EPAF-1635LC | Mouse Anti-ICAM1 Recombinant Antibody (clone c78.4A) | FC | Mouse IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
HPAB-0043-FY | Human Anti-ICAM1 Recombinant Antibody (clone Icmo0191) | ELISA | Human IgG1, λ |
HPAB-0859-CN | Human Anti-ICAM1 Recombinant Antibody (clone BI-AB) | ELISA, FC, Neut | Human IgG1 |
FN-206CQ | Rat Anti-Icam1 Recombinant Antibody (clone CBL-1338) | FC, FuncS, IHC-Fr, Neut, IP, IHC, WB | Rat IgG2a, κ |
HPAB-S0062-YC | Human Anti-ICAM1 Recombinant Antibody (clone HumB) | ELISA, FuncS | Humanized IgG |
HPAB-S0063-YC | Human Anti-ICAM1 Recombinant Antibody (clone HumC) | ELISA, FuncS | Humanized IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
HPAB-0859-CN-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone BI-AB); scFv Fragment | ELISA, FC, Neut | Human scFv |
HPAB-S0063-YC-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone HumC); scFv Fragment | ELISA, FuncS | Humanized scFv |
HPAB-S0064-YC-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone HumD); scFv Fragment | ELISA, FuncS | Humanized scFv |
HPAB-S0065-YC-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone HumF); scFv Fragment | ELISA, FuncS | Humanized scFv |
HPAB-S0066-YC-S(P) | Human Anti-ICAM1 Recombinant Antibody (clone HumH); scFv Fragment | ELISA, FuncS | Humanized scFv |
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