PF-06671008
PF-06671008 is a bispecific CD3/P-cadherin binding agent (Kd 11.4, 0.47 nM). PF-06671008 binds to the T cell receptor complex, activates polyclonal T cells, and forms a trimolecular complex that redirects T cells to P-cadherin-expressing tumor cells. PF-06671008 elicits P-cadherin-dependent T cell cytotoxicity across multiple indications. PF-06671008 causes increased tumor-infiltrating T cells in mice, achieves higher tumor exposure in PBMC-engrafted versus non-PBMC-engrafted mice by reducing internalization of P-cadherin-bound drug, and induces T cell-mediated tumor killing, elevated serum cytokines, tumor regression, as well as prolonged half-life and maintained exposure in tumor-bearing mice. PF-06671008 can be used in the research of solid tumors.
For research use only. We do not sell to patients.
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Species Reactivity
Human
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
1.36 nM
|
Binding of PF-06671008 to CHO cells overexpressing human P-cadherin by flow cytometry using APC-labeled F(ab')2 anti-human IgG-Fc antibody.
Binding of PF-06671008 to CHO cells overexpressing human P-cadherin by flow cytometry using APC-labeled F(ab')2 anti-human IgG-Fc antibody.
|
29067496 |
| CHO | EC50 |
0.41 pM
|
Cytotoxic T cell-mediated killing of P-cadherin-expressing CHO cells by PF-06671008 at a 10:1 E:T ratio with in vitro-expanded human CD3+ lymphocytes, assessed by luciferase activity on day 2.
Cytotoxic T cell-mediated killing of P-cadherin-expressing CHO cells by PF-06671008 at a 10:1 E:T ratio with in vitro-expanded human CD3+ lymphocytes, assessed by luciferase activity on day 2.
|
29067496 |
| HCC1954 | EC50 |
0.11 pM
|
Cytotoxic T cell-mediated killing of human HCC1954 tumor cells by PF-06671008 at a 3:1 E:T ratio with freshly isolated human CD3+ T cells, assessed by luciferase activity on day 3.
Cytotoxic T cell-mediated killing of human HCC1954 tumor cells by PF-06671008 at a 3:1 E:T ratio with freshly isolated human CD3+ T cells, assessed by luciferase activity on day 3.
|
29067496 |
| HT-29 | EC50 |
1.44 nM
|
Cytotoxic T cell-mediated killing of human HT29 tumor cells by PF-06671008 at a 3:1 E:T ratio with freshly isolated human CD3+ T cells, assessed by luciferase activity on day 3.
Cytotoxic T cell-mediated killing of human HT29 tumor cells by PF-06671008 at a 3:1 E:T ratio with freshly isolated human CD3+ T cells, assessed by luciferase activity on day 3.
|
29067496 |
In Vitro
PF-06671008 (48 h) mediated P-cadherin-dependent killing of P-cadherin-expressing CHO target cells by human CD3+ T cells, with an EC50 of 0.41 pM, whereas parental CHO cells were not killed[2].
PF-06671008 demonstrated potent cytotoxic T cell-mediated killing in human tumor cell lines expressing P-cadherin, with EC50 values ranging from 0.11 pM (HCC1954) to 1.44 nM (HT29), and correlated with P-cadherin receptor density[2].
PF-06671008 (48 h) induced dose-dependent activation of human CD4+ and CD8+ T cells in the presence of HCT116 tumor cells, with CD69 EC50 values of 4.45-4.87 nM and 4-1BB EC50 values of 13.7-17.9 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
PF-06671008 (0.05-0.5 mg/kg; i.v.; q7d × 3 or q7d × 5) achieved tumor stasis at a calculated tumor trimer TSC of 0.011 pM in HCT-116 adoptively transferred xenograft tumors[1].
PF-06671008 (0.05-0.5 mg/kg; i.v.; q7d × 3 or q7d × 5) achieved tumor stasis at a calculated tumor trimer TSC of 0.0092 pM in SUM-149 adoptive transfer xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD-scid IL-2rgnull (NSG) (female, 6-8-week-old)[1]
-
Dosage:0.01 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.15 mg/kg, and 0.5 mg/kg
-
Administration:i.v.; q7d × 2
-
Result:Calculated population median tumor stasis trimer concentration (TSC) in the HCT-116 T cell engrafted model was 0.064 pM.
Across the three mouse xenograft models, the geometric mean Ceff for tumor stasis was 0.028 pM.
-
Animal Model:NOD-scid IL-2rgnull (NSG) (8-10-week-old)[1]
-
Dosage:0.05 mg/kg, 0.15 mg/kg, and 0.5 mg/kg
-
Administration:i.v.; q7d × 3 or q7d × 5
-
Result:Calculated population median tumor stasis trimer concentration (TSC) in the HCT-116 adoptive transfer model was 0.011 pM.
-
Animal Model:NOD-scid IL-2rgnull (NSG) (8-10-week-old)[1]
-
Dosage:0.05 mg/kg, 0.15 mg/kg, and 0.5 mg/kg
-
Administration:i.v.; q7d × 3 or q7d × 5
-
Result:Calculated population median tumor stasis trimer concentration (TSC) in the SUM-149 adoptive transfer model was 0.0092 pM.
Target
CD3 & P-cadherin
Conjugated
Unconjugated
Application
ELISA, FACS, Functional assay
Chemical Information
-
SMILES
[PF-06671008]
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)