REGN2878
REGN2878 (PRLR ADC antibody) is a monoclonal antibody targeting the prolactin receptor (PRLR) and can block prolactin‑mediated activation of PRLR. REGN2878 exhibits an equilibrium dissociation constant (KD) of 1.05 nM and an IC50 of 0.344 nM for human PRLR. REGN2878 can be rapidly internalized and degraded in lysosomes by PRLR‑positive tumor cells, showing antigen‑specific binding and targeted enrichment properties. REGN2878 derivatives can be used as an immunoPET agent for antigen‑specific imaging of PRLR‑related tumors, and can also serve as a component of ADCs to exert anti‑tumor activity in breast cancer xenograft models. REGN2878 can be used in the research of breast cancer and prostate cancer. Isotype Comparison HY-P99001.
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
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Human IgG1 kappa
Human
REGN2878 (3.125-200 nM) binds human monomeric PRLR with high affinity (Kd = 1.05 nM) and monkey monomeric PRLR with similar high affinity, but does not bind rodent PRLR[1].
REGN2878 (520 pM-30 nM; 1 h) inhibits the binding of human PRLR to its ligand PRL in an ELISA-based assay with an IC50 of 5.0 nM[1].
REGN2878 (3.38 pM-200 nM; 5 h) potently inhibits PRL-induced PRLR-STAT5 signaling in engineered HEK293 reporter cells with an IC50 of 0.4 nM[1].
REGN2878 binds to cell surface PRLR on MCF7, MCF7/PRLR, and T47D breast cancer cell lines, with binding intensity correlating with PRLR expression levels[1].
REGN2878 potently inhibits 131I REGN2878 binding to MCF-7/PRLR cells with IC50 values of 0.344 nM (parental) and 0.3343 nM (127I-labeled), respectively, while DFO-conjugated REGN2878 shows a ratio-dependent increase in IC50[2].
REGN2878 (6.25-200 nM) binds human PRLR ectodomain with a Kd of 4.20 nM, and DFO-conjugated REGN2878 shows minimal ratio-dependent decreases in binding affinity[2].
REGN2878 (60 min) retains high immunoreactivity (67-120%) for PRLR expressed on MCF-7/PRLR cells[2].
REGN2878 specifically binds human PRLR ectodomain protein[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
When labeled with 89Zr (522 kBq-5.51 MBq (4.7-24 μg); intravenous injection; single dose), REGN2878 achieves specific tumor uptake in a low PRLR-expressing MCF-7 breast cancer xenograft model in female athymic nude mice[2].
89Zr-labeled REGN2878 (503 kBq-5.51 MBq (4.6-24 μg), with 2 mg of non-radioactive REGN2878; intravenous injection; single dose) achieves specific, blockable tumor uptake in the PC3/PRLR prostate cancer xenograft model of male CB17 SCID mice. Pre-administration of 2 mg non-radioactive REGN2878 reduces the uptake to 10.2 %IA/g at ~48 h[2].
When labeled with 89Zr (522 kBq-5.51 MBq, 4.7-24 μg, single intravenous dose), REGN2878 shows low tumor uptake in the PC3 prostate cancer xenograft model with extremely low PRLR expression in male CB17 SCID mice, while it achieves specific tumor uptake in the T47Dv11 breast cancer xenograft model with moderate PRLR expression in female CB17 SCID mice[2].
When labeled with 124I (4.81 MBq (34.2 μg); intravenous injection; single dose), REGN2878 exhibits extremely low tumor uptake and rapid systemic clearance in the MCF-7/PRLR breast cancer xenograft model of female athymic nude mice[2].
After labeling with 124I (725 kBq; intravenous injection; single co-injection), REGN2878 shows extremely low and continuously decreasing tumor uptake in MCF-7/PRLR breast cancer xenografts of female athymic nude mice, whereas 89Zr-REGN2878 (181 kBq; intravenous injection; single co-injection) exhibits high and continuously increasing tumor uptake[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:athymic nude mice (female)[2]
-
Dosage:522 kBq (4.7 μg) Zr-89 REGN2878 (biodistribution studies)
5.51 MBq (24 μg) Zr-89 REGN2878 (imaging studies) -
Administration:i.v.; single dose (biodistribution studies)
i.v.; single dose (imaging studies) -
Result:Reached a mean of 40.0%IA/g at 138 h post-injection.
Showed a mean tumor uptake of 16.4%IA/mL at ~140.8 h post-injection via imaging.
Exhibited low normal organ uptake, similar to uptake in mice with MCF-7/PRLR xenografts.\nReached a mean of partial tumor uptake data at 138 h post-injection, with full results incomplete.
-
Animal Model:CB17 SCID mice (male)[2]
-
Dosage:522 kBq (4.7 μg) Zr-89 REGN2878 (standard biodistribution studies)
5.51 MBq (24 μg) Zr-89 REGN2878 (imaging studies)
2 mg nonradioactive REGN2878 + 503 kBq (4.6 μg) Zr-89 REGN2878 (blocking studies) -
Administration:i.v.; single dose (standard biodistribution studies)
i.v.; single dose (imaging studies)
i.v.; single dose (blocking studies) -
Result:Reached a mean of 27.1%IA/g at 138 h post-injection without pre-blocking.
Showed a mean tumor uptake of 27.4%IA/mL at ~143 h post-injection via imaging.
Reduced tumor uptake to a mean of 10.2%IA/g at ~48 h post-injection with pre-administration of 2 mg nonradioactive REGN2878, while unblocked tumor uptake at ~48 h post-injection was a mean of 25.2%IA/g.
Exhibited blocked tumor uptake similar to uptake in low PRLR-expressing PC3 xenografts.
-
Animal Model:CB17 SCID mice (male)[2]
-
Dosage:522 kBq (4.7 μg) Zr-89 REGN2878 (biodistribution studies)
5.51 MBq (24 μg) Zr-89 REGN2878 (imaging studies) -
Administration:i.v.; single dose (biodistribution studies)
i.v.; single dose (imaging studies) -
Result:Reached a mean of 7.6%IA/g at 138 h post-injection.
Showed a mean tumor uptake of 6.3%IA/mL at ~142.6 h post-injection via imaging.
Exhibited low normal organ uptake.
-
Animal Model:CB17 SCID mice (female)[2]
-
Dosage:522 kBq (4.7 μg) Zr-89 REGN2878 (biodistribution studies)
5.51 MBq (24 μg) Zr-89 REGN2878 (imaging studies) -
Administration:i.v.; single dose (biodistribution studies)
i.v.; single dose (imaging studies) -
Result:Reached a mean of 29.6%IA/g at 138 h post-injection.
Showed a mean tumor uptake of 34.0%IA/mL at ~143 h post-injection via imaging.
Exhibited low normal organ uptake.
PRLR/Prolactin Receptor
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
-
Product Image
ELISA, FACS, Functional assay
Chemical Information
-
Synonyms
PRLR ADC antibody
-
Formulation
Please refer to the lot-specific COA for specific buffer information.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Kelly MP, et al. Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers. Mol Cancer Ther. 2017;16(7):1299-1311. [Content Brief]
[2]. Cheal SM, et al. ImmunoPET Imaging of Endogenous and Transfected Prolactin Receptor Tumor Xenografts. Mol Pharm. 2018;15(6):2133-2141. [Content Brief]
[3]. Anderson MG, et al. ABBV-176, a PRLR antibody drug conjugate with a potent DNA-damaging PBD cytotoxin and enhanced activity with PARP inhibition. BMC Cancer. 2021;21(1):681. Published 2021 Jun 9. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Powered by Bioz