Emerging new therapeutic antibody derivatives for cancer treatment

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Abstract

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells. The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies, such as antibody fragments, bispecific antibodies, and antibody derivatives (e.g., antibody–drug conjugates and immunocytokines). The miniaturization and multifunctionalization of antibodies are flexible and viable strategies for diagnosing or treating malignant tumors in a complex tumor environment. In this review, we summarize antibodies of various molecular types, antibody applications in cancer therapy, and details of clinical study advances. We also discuss the rationale and mechanism of action of various antibody formats, including antibody–drug conjugates, antibody–oligonucleotide conjugates, bispecific/multispecific antibodies, immunocytokines, antibody fragments, and scaffold proteins. With advances in modern biotechnology, well-designed novel antibodies are finally paving the way for successful treatments of various cancers, including precise tumor immunotherapy, in the clinic.

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez … (2019)

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Cancer genome landscapes.

Bert Vogelstein, Nickolas Papadopoulos, Victor E Velculescu … (2013)

Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of "mountains" (genes altered in a high percentage of tumors) and a much larger number of "hills" (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or "drive" tumorigenesis. A typical tumor contains two to eight of these "driver gene" mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

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Author and article information

Contributors

Shuqing Chen: chenshuqing@zju.edu.cn

Liqiang Pan: panliqiang@zju.edu.cn

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 7 February 2022

Publication date PMC-release: 7 February 2022

Publication date Collection: 2022

Volume: 7

Electronic Location Identifier: 39

Affiliations

[1 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, , Zhejiang University, ; 310058 Hangzhou, China

[2 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Precision Medicine on Tumor Therapeutics, , ZJU-Hangzhou Global Scientific and Technological Innovation Center, ; 311200 Hangzhou, China

[3 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; 310003 Hangzhou, China

[4 ]Key Laboratory of Pancreatic Disease of Zhejiang Province, 310003 Hangzhou, China

Article

Publisher ID: 868

DOI: 10.1038/s41392-021-00868-x

PMC ID: 8821599

PubMed ID: 35132063

SO-VID: af90ce83-856d-4ac6-bb63-f5d7a72de9aa

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 2 April 2021

Date revision received : 14 December 2021

Date accepted : 16 December 2021

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 82073750

Award Recipient : Shuqing Chen Liqiang Pan

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Keywords: drug delivery,drug development

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Keywords: drug delivery, drug development

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Emerging new therapeutic antibody derivatives for cancer treatment

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Most cited references 398

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

Cancer genome landscapes.

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Cited by 67

Most referenced authors 7,261