Development Trends for Human Monoclonal Antibody Therapeutics

Overview

Journal Nat Rev Drug Discov

Specialty Pharmacology

Date 2010 Sep 3

PMID 20811384

Citations 372

Authors

Aaron L Nelson

Eugen Dhimolea

Janice M Reichert

Affiliations

Soon will be listed here.

Abstract

Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study - in particular, transgenic mice and yeast or phage display - renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.

Citing Articles

PROPERMAB: an integrative framework for prediction of antibody developability using machine learning.

Li B, Luo S, Wang W, Xu J, Liu D, Shameem M MAbs. 2025; 17(1):2474521.

PMID: 40042626 PMC: 11901398. DOI: 10.1080/19420862.2025.2474521.

Monoclonal Antibodies in Metastatic Gastro-Esophageal Cancers: An Overview of the Latest Therapeutic Advances.

Kalofonou F, Kalofonou M, Dimitrakopoulos F, Kalofonos H Int J Mol Sci. 2025; 26(3).

PMID: 39940858 PMC: 11816984. DOI: 10.3390/ijms26031090.

From Lab to Clinic: Effect of Academia-Industry Collaboration Characteristics on Oncology Phase 1 Trial Entry.

Yang W, Lee S Clin Transl Sci. 2025; 18(1):e70135.

PMID: 39807955 PMC: 11730079. DOI: 10.1111/cts.70135.

Single-Stranded Variable Fragment Gene Libraries Built for Phage Display: An Updated Review of Design, Selection and Application.

de Souza C, Gloria J, da Silva E, de Lima Guerra Corado A, de Alcantara K, Cordeiro I J Microbiol Biotechnol. 2024; 35:e2407049.

PMID: 39631781 PMC: 11813352. DOI: 10.4014/jmb.2407.07049.

Learning antibody sequence constraints from allelic inclusion.

Jagota M, Hsu C, Mazumder T, Sung K, DeWitt W, Listgarten J bioRxiv. 2024; .

PMID: 39484623 PMC: 11526943. DOI: 10.1101/2024.10.22.619760.

References

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

McCafferty J, Griffiths A, Winter G, Chiswell D . Phage antibodies: filamentous phage displaying antibody variable domains. Nature. 1990; 348(6301):552-4. DOI: 10.1038/348552a0. View

De Groot A, Scott D . Immunogenicity of protein therapeutics. Trends Immunol. 2007; 28(11):482-90. DOI: 10.1016/j.it.2007.07.011. View

Zhang B . Ofatumumab. MAbs. 2010; 1(4):326-31. PMC: 2726602. DOI: 10.4161/mabs.1.4.8895. View

Clackson T, Hoogenboom H, Griffiths A, Winter G . Making antibody fragments using phage display libraries. Nature. 1991; 352(6336):624-8. DOI: 10.1038/352624a0. View

Cross A . Antiendotoxin antibodies: a dead end?. Ann Intern Med. 1994; 121(1):58-60. DOI: 10.7326/0003-4819-121-1-199407010-00011. View

Lachmann H, Kone-Paut I, Kuemmerle-Deschner J, Leslie K, Hachulla E, Quartier P . Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009; 360(23):2416-25. DOI: 10.1056/NEJMoa0810787. View

Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B . Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25(13):1658-64. DOI: 10.1200/JCO.2006.08.1620. View

Vaughan T, Williams A, Pritchard K, Osbourn J, Pope A, Earnshaw J . Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol. 1996; 14(3):309-14. DOI: 10.1038/nbt0396-309. View

10.

Green L . Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J Immunol Methods. 2000; 231(1-2):11-23. DOI: 10.1016/s0022-1759(99)00137-4. View

11.

Shankar G, Pendley C, Stein K . A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs. Nat Biotechnol. 2007; 25(5):555-61. DOI: 10.1038/nbt1303. View

12.

Emmi L, Chiarini F . The role of intravenous immunoglobulin therapy in autoimmune and inflammatory disorders. Neurol Sci. 2002; 23 Suppl 1:S1-8. DOI: 10.1007/s100720200010. View

13.

Teng N, Kaplan H, Hebert J, Moore C, Douglas H, Wunderlich A . Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci U S A. 1985; 82(6):1790-4. PMC: 397358. DOI: 10.1073/pnas.82.6.1790. View

14.

Lecluse L, Driessen R, Spuls P, de Jong E, Stapel S, van Doorn M . Extent and clinical consequences of antibody formation against adalimumab in patients with plaque psoriasis. Arch Dermatol. 2010; 146(2):127-32. DOI: 10.1001/archdermatol.2009.347. View

15.

Green L, Hardy M, Tsuda H, Louie D, Mendez M, Abderrahim H . Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nat Genet. 1994; 7(1):13-21. DOI: 10.1038/ng0594-13. View

16.

JAMES K, Bell G . Human monoclonal antibody production. Current status and future prospects. J Immunol Methods. 1987; 100(1-2):5-40. DOI: 10.1016/0022-1759(87)90170-0. View

17.

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

18.

Reichert J, Rosensweig C, Faden L, Dewitz M . Monoclonal antibody successes in the clinic. Nat Biotechnol. 2005; 23(9):1073-8. DOI: 10.1038/nbt0905-1073. View

19.

Pageau S . Denosumab. MAbs. 2010; 1(3):210-5. PMC: 2726593. DOI: 10.4161/mabs.1.3.8592. View

20.

Hwang W, Foote J . Immunogenicity of engineered antibodies. Methods. 2005; 36(1):3-10. DOI: 10.1016/j.ymeth.2005.01.001. View