Looking for the Optimal PD-1/PD-L1 Inhibitor in Cancer Treatment: A Comparison in Basic Structure, Function, and Clinical Practice

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Jun 18

PMID 32547566

Citations 41

Authors

Yu Chen

Yanqing Pei

Jingyu Luo

Zhaoqin Huang

Jinming Yu

Xiangjiao Meng

Affiliations

Soon will be listed here.

Abstract

Programmed cell death protein-1/ligand 1 (PD-1/L1) targeted immune checkpoint inhibitors have become the focus of tumor treatment due to their promising efficacy. Currently, several PD-1/PD-L1 inhibitors have been approved for clinical practice with several more in clinical trials. Notably, based on available trial data, the selection of different PD-1/PD-L1 inhibitors in the therapeutic application and the corresponding efficacy varies. Widespread attention then is increasingly raised to the clinical comparability of different PD-1/PD-L1 inhibitors. The comparison of the inhibitors could not only help clinicians make in-depth understanding of them, but also further facilitate the selection of the optimal inhibitor for patients in treatment as well as for future clinical research and the development of new related drugs. As we all know, molecular structure could determine molecular function, which further affects their application. Therefore, in this review, we aim to comprehensively compare the structural basis, molecular biological functions, and clinical practice of different PD-1/PD-L1 inhibitors.

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References

Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F . Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018; 19(11):1468-1479. DOI: 10.1016/S1470-2045(18)30673-9. View

Yang D, Kroe-Barrett R, Singh S, Roberts C, Laue T . IgG cooperativity - Is there allostery? Implications for antibody functions and therapeutic antibody development. MAbs. 2017; 9(8):1231-1252. PMC: 5680800. DOI: 10.1080/19420862.2017.1367074. View

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

Sui H, Ma N, Wang Y, Li H, Liu X, Su Y . Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies. J Immunol Res. 2018; 2018:6984948. PMC: 6109480. DOI: 10.1155/2018/6984948. View

Aalberse R, Stapel S, Schuurman J, Rispens T . Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009; 39(4):469-77. DOI: 10.1111/j.1365-2222.2009.03207.x. View

Francisco L, Sage P, Sharpe A . The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010; 236:219-42. PMC: 2919275. DOI: 10.1111/j.1600-065X.2010.00923.x. View

Pardoll D . The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4):252-64. PMC: 4856023. DOI: 10.1038/nrc3239. View

Fu J, Wang F, Dong L, Deng C, Wang X, Xie X . Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017; 38(5):710-718. PMC: 5457696. DOI: 10.1038/aps.2016.161. View

Harding F, Stickler M, Razo J, DuBridge R . The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010; 2(3):256-65. PMC: 2881252. DOI: 10.4161/mabs.2.3.11641. View

10.

Socinski M, Jotte R, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N . Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301. DOI: 10.1056/NEJMoa1716948. View

11.

Rosenberg J, Hoffman-Censits J, Powles T, van der Heijden M, Balar A, Necchi A . Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-20. PMC: 5480242. DOI: 10.1016/S0140-6736(16)00561-4. View

12.

Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015; 387(10027):1540-1550. DOI: 10.1016/S0140-6736(15)01281-7. View

13.

Almagro J, Daniels-Wells T, Perez-Tapia S, Penichet M . Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy. Front Immunol. 2018; 8:1751. PMC: 5770808. DOI: 10.3389/fimmu.2017.01751. View

14.

Liu K, Tan S, Chai Y, Chen D, Song H, Zhang C . Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy. Cell Res. 2016; 27(1):151-153. PMC: 5223223. DOI: 10.1038/cr.2016.102. View

15.

Aalberse R, Schuurman J . IgG4 breaking the rules. Immunology. 2002; 105(1):9-19. PMC: 1782638. DOI: 10.1046/j.0019-2805.2001.01341.x. View

16.

Duan J, Cui L, Zhao X, Bai H, Cai S, Wang G . Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2019; 6(3):375-384. PMC: 6990765. DOI: 10.1001/jamaoncol.2019.5367. View

17.

Sheng J, Srivastava S, Sanghavi K, Lu Z, Schmidt B, Bello A . Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors. J Clin Pharmacol. 2017; 57 Suppl 10:S26-S42. DOI: 10.1002/jcph.990. View

18.

Xu C, Chen Y, Du X, Liu J, Huang C, Chen L . Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ. 2018; 363:k4226. PMC: 6222274. DOI: 10.1136/bmj.k4226. View

19.

Salfeld J . Isotype selection in antibody engineering. Nat Biotechnol. 2007; 25(12):1369-72. DOI: 10.1038/nbt1207-1369. View

20.

Keir M, Butte M, Freeman G, Sharpe A . PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008; 26:677-704. PMC: 10637733. DOI: 10.1146/annurev.immunol.26.021607.090331. View