Cell lines

MCF7 human breast cancer cell line

Preparation Method

Various concentrations of nivolumab (0, 2, 4, 8, 16, and 32 nM) and OCT4&SOX2 CTLs with an effector-target ratio of 20:1 were used to treat MCF7 BCSCs for 24 h; cell proliferation was detected busing the CCK-8 assay.

Reaction Conditions

0, 2, 4, 8, 16, and 32 nM; 24 h

Applications

Nivolumab improved the cytotoxic activity of OCT4&SOX2 CTLs against MCF7 BCSCs in a dose-dependent manner by the CCK-8 assay.

Animal models

cynomolgus macaques

Preparation Method

In a single-dose pharmacokinetic study, cynomolgus monkeys (Macaca fascicularis) received i.v. nivolumab, 1 mg/kg (3 males and 3 females) or 10 mg/kg (3 males).

Dosage form

1 mg/kg or 10 mg/kg; i.v.

Applications

Single, i.v. administration of nivolumab to cynomolgus monkeys at 1 and 10 mg/kg was well tolerated with no effects on body weight or clinical observations.

• Clin Transl Med 12.6 (2022): e901.PMID:35696531
• J Oncol 2022 (2022).

Nivolumab, an anti-cancer monoclonal antibody, is a programmed death receptor-1 blocking human IgG4 antibody to treat advanced (metastatic) non-small cell lung cancer.^[1]

In vitro efficacy test it shown that Nivolumab bound to CHO cells expressing PD-1 with an EC50 of 1.66 nmol/L and bound to PD-1 on activated T cells with an EC50 of 0.64 nmol/L. In the meanwhile, Nivolumab can inhibit the interaction between PD-1 and its ligands, PD-L1 and PD-L2, with IC50 values of 2.52 and 2.59 nmol/L, respectively. In vitro, at 1.5 ng/mL concentrations of nivolumab enhances T-cell reactivity in the presence of a T-cell receptor stimulus.^[1]

In vivo study it indicated that mice were treated with 50 mg/kg nivolumab, there were no changes in T3, T4, or TSH levels. After administration of 10 mg/kg and 50 mg/kg nivolumab in cynomolgus monkeys, the results shown that there were dramatically more CD8+ effector memory T cells in the 50 mg/kg group than in the 10 mg/kg and untreated groups and Naive T-cell populations were decreased in the 50 mg/kg group.^[1]In vivo, Nivolumab treatment (30 mg/kg, i.p.) inhibits growth of the TNBC MDA-MB-231 cell line in hu-CB-BRGS mice.^[3]BLT-NOG-EXL mice treated with either saline, 2.5, 5, or 10 mg/kg of nivolumab i.p. for 28 days, the results demonstrated a dose-dependent relationship in mortality.^[4]In vivo test it suggested that anti-PD-1 treatment with Nivolumab (10 mg/kg, i.v.) diminishes morphine antinociception in wild-type mice.^[5]

References:
[1].Wang C, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014 Sep;2(9):846-56.
[2].Ramos-Levi AM, et al. Nivolumab-induced thyroid dysfunction in patients with lung cancer. Endocrinol Diabetes Nutr (Engl Ed). 2019 Jan;66(1):26-34. English, Spanish.
[3].Capasso A, et al. Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts. J Immunother Cancer. 2019 Feb 8;7(1):37.
[4].Weaver JL, et al. BLT-Immune Humanized Mice as a Model for Nivolumab-Induced Immune-Mediated Adverse Events: Comparison of the NOG and NOG-EXL Strains. Toxicol Sci. 2019 May 1;169(1):194-208.
[5].Wang Z, et al. Anti-PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates. Sci Transl Med. 2020 Feb 19;12(531):eaaw6471.