Dataset Information

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions.

ABSTRACT: The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody-drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted HER2 therapy, which has doubled the number of patients who can benefit from these treatments. However, despite the initial enthusiasm, there are still several problems in this field represented by drug resistance and tumor recurrence that require the further development of new more efficient drugs. In this review, we discuss various approaches for targeting the HER2 molecule in cancer treatment, highlighting their benefits and drawbacks, along with the different mechanisms responsible for resistance to HER2-targeted therapies and how to overcome them.

SUBMITTER: Alrhmoun S

PROVIDER: S-EPMC9776683 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions.

Alrhmoun Saleh S Sennikov Sergey S

Cancers 20221214 24

The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody-drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted ...[more]

PMID: 36551661

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Project description:BackgroundRecent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells. Today, it has become possible to isolate CTLs specific for certain antigenic determinants from heterogeneous populations of mononuclear cells. This enables direct and specific cell-mediated immune responses against cells carrying certain antigens. The aim of the present study was to develop an optimized protocol for generating CTL populations specific for epitopes of tumor-associated antigen HER2/neu, and to assess their cytotoxic effects against the HER2/neu-expressing MCF-7 tumor cell line.MethodsThe developed protocol included sequential stages of obtaining mature DCs from PBMCs from HLA A*02-positive healthy donors, magnet-assisted transfection of mature DCs with the pMax plasmid encoding immunogenic peptides HER2 p369-377 (E75 peptide) and HER2 p689-697 (E88 peptide), coculture of antigen-activated DCs with autologous lymphocytes, magnetic-activated sorting of CTLs specific to HER2 epitopes, and stimulation of isolated CTLs with cytokines (IL-2, IL-7, and IL-15).ResultsThe resulting CTL populations were characterized by high contents of CD8+ cells (71.5% in cultures of E88-specific T cells and 90.2% in cultures of E75-specific T cells) and displayed strong cytotoxic effects against the MCF-7 cell line (percentages of damaged tumor cells in samples under investigation were 60.2 and 65.7% for E88- and E75-specific T cells, respectively; level of spontaneous death of target cells was 17.9%).ConclusionsThe developed protocol improves the efficiency of obtaining HER2/neu-specific CTLs and can be further used to obtain cell-based vaccines for eradicating targeted tumor cells to prevent tumor recurrence after the major tumor burden has been eliminated and preventing metastasis in patients with HER2-overexpressing tumors.

Project description:The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease. Current strategies to decrease a woman's risk of developing breast cancer include primary prevention, such as avoiding tobacco, exogenous hormone use and excess exposure to ionizing radiation, maintaining a normal weight, exercise, breastfeeding, eating a healthy diet and minimizing alcohol intake. Chemoprevention medications are available for those at high risk, though they are underutilized in eligible women. Mastectomy and/or bilateral oophorectomy are reasonable strategies for women who have deleterious mutations in genes that dramatically increase the risk of developing cancer in either breast. There are a variety of strategies in development for the prevention of breast cancer. Personalized approaches to prevent breast cancer that are being developed focus on advances in precision medicine, knowledge of the immune system and the tumor microenvironment and their role in cancer development. Advances in our understanding of how breast cancer develops are allowing investigators to specifically target populations who are most likely to benefit. Additionally, prevention clinical trials are starting to evaluate multi-agent cancer prevention approaches, with the hope of improved efficacy over single agents. Finally, there is a push to increase the use of chemopreventive agents with proven efficacy, such as tamoxifen and raloxifene, in the prevention of breast cancer.

Dataset Information

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions.

Publications

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions.

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