» Articles » PMID: 38956700

Targeting Cytotoxic Lymphocyte Antigen 4 (CTLA-4) in Breast Cancer

Overview
Journal Eur J Med Res
Publisher Biomed Central
Specialty General Medicine
Date 2024 Jul 3
PMID 38956700
Authors
Affiliations
Soon will be listed here.
Abstract

Breast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift occurred with the discovery of tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in the BC tumor microenvironment. CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) immunotherapy has emerged as a treatment option for BC, but it has limitations, including suboptimal antitumor effects and toxicity. Research has demonstrated that anti-CTLA-4 combination therapies, such as Treg depletion, cancer vaccines, and modulation of the gut microbiome, are significantly more effective than CTLA-4 monoclonal antibody (mAB) monotherapy. Second-generation CTLA-4 antibodies are currently being developed to mitigate immune-related adverse events (irAEs) and augment antitumor efficacy. This review examines anti-CTLA-4 mAB in BC, both as monotherapy and in combination with other treatments, and sheds light on ongoing clinical trials, novel CTLA-4 therapeutic strategies, and potential utility of biomarkers in BC.

Citing Articles

Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.

Nedeljkovic M, Vuletic A, Mirjacic Martinovic K Int J Mol Sci. 2025; 26(4).

PMID: 40003864 PMC: 11855393. DOI: 10.3390/ijms26041396.


Prognostic impact of metformin in solid cancer patients receiving immune checkpoint inhibitors: novel evidences from a multicenter retrospective study.

Wang J, Lin J, Guo H, Wu W, Yang J, Mao J Front Pharmacol. 2024; 15:1419498.

PMID: 39135791 PMC: 11317293. DOI: 10.3389/fphar.2024.1419498.

References
1.
Autio K, Boni V, Humphrey R, Naing A . Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology. Clin Cancer Res. 2019; 26(5):984-989. PMC: 8436251. DOI: 10.1158/1078-0432.CCR-19-1457. View

2.
Song Y, Lai L, Chong Z, He J, Zhang Y, Xue Y . E3 ligase FBXW7 is critical for RIG-I stabilization during antiviral responses. Nat Commun. 2017; 8:14654. PMC: 5355826. DOI: 10.1038/ncomms14654. View

3.
Disis M, Stanton S . Triple-negative breast cancer: immune modulation as the new treatment paradigm. Am Soc Clin Oncol Educ Book. 2015; :e25-30. DOI: 10.14694/EdBook_AM.2015.35.e25. View

4.
Mediratta K, El-Sahli S, DCosta V, Wang L . Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer. Cancers (Basel). 2020; 12(12). PMC: 7761500. DOI: 10.3390/cancers12123529. View

5.
Galluzzi L, Humeau J, Buque A, Zitvogel L, Kroemer G . Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020; 17(12):725-741. DOI: 10.1038/s41571-020-0413-z. View