Penpulimab
(Synonyms: 派安普利单抗) 目录号 : GC66394
Penpulimab 是一种 IgG1 抗 PD-1 单克隆抗体，具有抗肿瘤活性。
Cas No.:2350298-92-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Penpulimab is an IgG1 backbone anti-PD-1 monoclonal antibody with antitumor activities[1].
Penpulimab demonstrates better stability and a lower level of host-cell protein residue compared with IgG4 backbone anti-PD-1 antibodies[1].
Penpulimab does not mediate complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC) and induces no remarkable IL-6 and IL-8 release by activated macrophages[1].
Penpulimab exhibits slower binding off-rate for human PD-1 than Nivolumab and Pembrolizumab [1].
Penpulimab potentiates T cell activation via PD-1/PD-L1 blockade[1].
Penpulimab (5 mg/kg; i.p.; twice a week, 3weeks) inhibits tumor growth in mice[2].
| Animal Model: | MC38-hPD-L1 tumor-bearing B-hPD-1 humanized mouse model[2] |
| Dosage: | 5 mg/kg |
| Administration: | IP, twice a week, 3weeks |
| Result: | Showed moderate inhibition of tumor growth (tumor volume: 58.4% of control group). Treatment combined with anlotinib (1 mg/kg, every day, p.o) significantly decreased tumor volume to 36.5% of control group. |
| Cas No. | 2350298-92-7 | SDF | Download SDF |
| 别名 | 派安普利单抗 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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Penpulimab: First Approval
Drugs 2021 Dec;81(18):2159-2166.PMID:34813051DOI:10.1007/s40265-021-01640-9.
Penpulimab (®) is a humanised anti-programmed cell death 1 (PD-1) monoclonal antibody developed by Akeso Biopharma, in collaboration with Chia Tai Tianqing (a subsidiary of SinoBiopharm), for the treatment of various cancers, including Hodgkin's lymphoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC) and solid tumours. Penpulimab is an immunoglobulin G1 monoclonal antibody engineered to completely eliminate Fcγ receptor binding and Fc-mediated effector functions that can compromise anti-tumour activity. In August 2021, Penpulimab received its first approval in China for the treatment of adult patients with relapsed or refractory classic Hodgkin's lymphoma who have undergone at least second-line chemotherapy. Penpulimab is under regulatory review for nasopharyngeal cancer and NSCLC in China. Clinical studies of Penpulimab are underway for various cancers in China and Australia. This article summarizes the milestones in the development of Penpulimab leading to this first approval for relapsed or refractory classic Hodgkin's lymphoma.
Antibodies to watch in 2022
MAbs 2022 Jan-Dec;14(1):2014296.PMID:35030985DOI:10.1080/19420862.2021.2014296.
In this 13th annual installment of the annual 'Antibodies to Watch' article series, we discuss key events in commercial antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. Regulatory review of antibody therapeutics that target the SARS-CoV-2 coronavirus proceeded at an unprecedented pace in 2021, resulting in both emergency use authorizations and full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well as others, in numerous countries. As of November 1, a total of 11 antibody therapeutics had been granted first approvals in either the United States or European Union in 2021 (evinacumab, dostarlimab loncastuximab tesirine, amivantamab, aducanumab, tralokinumab, anifrolumab, bimekizumab, tisotumab vedotin, regdanvimab, REGEN-COV2). The first global approvals of seven products, however, were granted elsewhere, including Japan (pabinafusp alfa), China (disitamab vedotin, Penpulimab, zimberelimab), Australia (sotrovimab, REGEN-COV2), or the Republic of Korea (regdanvimab). Globally, at least 27 novel antibody therapeutics are undergoing review by regulatory agencies. First actions by the Food and Drug Administration on the biologics license applications for faricimab, sutimlimab, tebentafusp, relatlimab, sintilimab, ublituximab and tezepelumab are expected in the first quarter of 2022. Finally, our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year. Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022.
Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers
Cancer Immunol Immunother 2022 Oct;71(10):2371-2379.PMID:35165764DOI:10.1007/s00262-022-03160-1.
Background: The safety and anti-tumor activity of Penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study. Methods: Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of Penpulimab. In the Phase Ia/Ib trial in Australia, patients received Penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg Penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of Penpulimab in patients with UGI cancers in these two trials were evaluated. Results: A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received Penpulimab with a median of 6 (1-64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date. Conclusions: Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted. Trial registration: Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506).
Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events
Front Immunol 2022 Jun 27;13:924542.PMID:35833116DOI:10.3389/fimmu.2022.924542.
Background: IgG4 anbibodies are deficient in stability and may contribute to tumor-associated escape from immune surveillance. We developed an IgG1 backbone anti-programmed cell death protein-1 (PD-1) antibody, Penpulimab, which is designed to remove crystallizable fragment (Fc) gamma receptor (FcγR) binding that mediates antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and proinflammatory cytokine release. Methods: Aggregation of different anti-PD-1 antibodies was tested by size exclusion chromatography, and melting temperature midpoint (Tm) and aggregation temperature onset (Tagg) were also determined. The affinity constants of Penpulimab for PD-1 and human FcγRs were measured by surface plasmon resonance and biolayer interferometry. ADCC and ADCP were determined in cellular assays and antibody-dependent cytokine release (ADCR) from human macrophages was detected by ELISA. Binding kinetics of Penpulimab to human PD-1 was determined by Biacore, and epitope/paratope mapping of PD-1/Penpulimab was investigated using x-ray crystallography. Additionally, patients from six ongoing trials were included for analysis of immune-related adverse events (irAEs). Results: Penpulimab demonstrated better stability and a lower level of host-cell protein residue compared with IgG4 backbone anti-PD-1 antibodies. As expected, Penpulimab exhibited no apparent binding to FcγRIa, FcγRIIa_H131, FcγRIIIa_V158 and FcγRIIIa_F158, elicited no apparent ADCC and ADCP activities, and induced no remarkable IL-6 and IL-8 release by activated macrophages in vitro. Penpulimab was shown in the co-crystal study to bind to human PD-1 N-glycosylation site at N58 and had a slower off-rate from PD-1 versus nivolumab or pembrolizumab. Four hundred sixty-five patients were analyzed for irAEs. Fifteen (3.2%) patients had grade 3 or above irAEs. No death from irAEs was reported. Conclusions: IgG1 backbone anti-PD1 antibody Penpulimab has a good stability and reduced host cell protein residue, as well as potent binding to the antigen. Fc engineering has eliminated Fc-mediated effector functions of Penpulimab including ADCC, ADCP and reduced ADCR, which may contribute to its more favorable safety profile. Clinical trial registration: www.ClinicalTrials.gov, identifier: AK105-101: NCT03352531, AK105-201: NCT03722147, AK105-301: NCT03866980, AK105-202:NCT03866967, AK105-203: NCT04172571, AK105-204: NCT04172506.
Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203)
Front Oncol 2021 Jul 13;11:684867.PMID:34327136DOI:10.3389/fonc.2021.684867.
Objective: This study aims to assess the efficacy and safety of Penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC. Methods: In this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18-75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child-Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received Penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571). Results: At the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4-22.1). The ORR was 31.0% (95% CI, 15.3-50.8%), and the DCR was 82.8% (95% CI, 64.2-94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0-12.3) and 8.8 months (95% CI, 4.0-12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9-82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs). Conclusion: Penpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.