• info@icbcongress.com
• English
• Persian

• Login

Create Free Account

INTERNATIONAL CONGRESS OF

CancerGenetics

• Targeting Breast Cancer Stem Cells with CAR-T Cells: A Novel Approach

• Aida Kamran ,^1,* Masha Nahavandi ,² Vahide Keyvani ,³
  1. Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
  2. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  3. Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
  
  
  
• Introduction: Breast cancer is one of the most common and lethal malignancies affecting women worldwide. Breast cancer stem cells (BCSCs) play an important role in tumorigenesis, development, metastasis, and recurrence. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Fundamentally, cancer stem cells represent a rare population of cancer cells, likely originating from non-malignant stem or progenitor cells, with the ability to evade immune surveillance and develop resistance to immunotherapeutic treatments. Chimeric Antigen Receptor (CAR-T) cell therapy is an immunotherapy type derived from adoptive T cell relocation. CAR-T cells are well equipped with specific antibodies to identify antigens in autologous tumor cells, thus bringing out cytotoxic outcomes. CARs are the modified receptors with improved specificity and responsiveness to enhance the recognition of cancer cells
• Methods: This review was conducted by analyzing articles published in PubMed, Google Scholar and Science Direct between 2021 and September 2025. The search keywords included ‘Breast Cancer Stem Cells’, ‘CAR-T Cells’, and ‘Breast Cancer’. A search of these three databases, more than 50 articles were reviewed. After screening titles and abstracts 30 were excluded based on predefined inclusion criteria, leaving 20 articles for full‑text review. Only English-language articles were included in this analysis.
• Results: Finally, 30 articles were selected in the study. Many studies have revealed the molecular process that leads to the emergence of breast cancer entails the active proliferation of epithelial cells of the breast tissue resulting in the formation of malignant cells in the ductal or lobular compartment of the breast. The hormone and growth factor receptors employed for breast cancer classification include estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Based on the expression or lack of expression of these receptors and the expression rate of Ki-67, there are four subtypes of breast cancer including Luminal A, Luminal B, HER2 amplified, and triple-negative breast cancer (TNBC). The first three subtypes are easier to manage since the patients with these subtypes are eligible for antibody-based therapies such as anti-HER2 monoclonal antibodies (mAbs) or antibody-drug conjugates (ADCs), tyrosine kinase inhibitors, and endocrine therapies (including ER degraders). Dissimilar from these subtypes, TNBC is a heterogeneous type of basal-like tumor that does not express the abovementioned receptors and it represents about 15 to 20% of all breast cancer cases. Recently, many studies demonstrate that the tumor microenvironment (TME) is dominated by immunosuppressive cytokines, including interleukin-10 (IL-10), transforming growth factorβ (TGFβ), and IL-35. Notably, IL-35 is produced by regulatory T cells and breast cancer cells and the conversion of conventional T cells into IL-35-producing induced regulatory T cells, along with the inhibition of pro-inflammatory cytokine secretion, contributes to the suppression of anti-tumor immunity. Additionally, immune checkpoint molecules—such as PD-1, PDL1, CTLA-4, TIM-3, LAG-3, and TIGIT—are upregulated within the TME, leading to T-cell exhaustion and diminished immune responses. In this case, researchers have the blockade of these checkpoints is shown to restore T-cell functionality and is proposed as a strategy to target tumor stem cells and convert the cold tumors into hot ones with robust effector cell infiltration. Moreover, T-cell-redirecting bispecific antibodies (TRBAs) have also been under investigation as candidates for the treatment of TNBC. CAR-T cells have the ability to recognize specific cancer stemness markers and efficiently eradicate CSCs while sparing normal stem cells (NSCs). Also the therapeutic potential of chimeric antigen receptor (CAR)T cell therapy with targeting specific tumor-associated antigens, such as glycoproteins and receptor tyrosine kinases, is highlighted. However, Combinatorial CAR-T therapy with other types of therapies can result in improved clinical outcomes of CAR-T therapy in TNBC. For instance, ECM- or CAF-targeting agents can be applied for maximizing CAR-T antitumor effects. Furthermore, macrophage- or monocyte-eliminating agents are beneficial for amplifying the tumoricidal impact of CAR-Ts, or anti-angiogenic agents can be leveraged for enhancing the tumor site trafficking of CAR-Ts. In this regard, γδ-CAR-Ts and CAR-expressing NK cells (CAR-NKs) have been investigated for the treatment of both hematologic and solid malignancies, and destruction of toumor stem cells TNBC. Such alternative CAR-expressing effector cells might be beneficial for tackling various types of CAR-T therapy challenges
• Conclusion: It is concluded that by targeting the metabolic and immunological pathways that support immune suppression – through combined strategies including checkpoint blockade, CAR-T cell therapies and combination therapies and we can overcome tumor stem cells and ultimately improving the overall efficacy of immunotherapies
• Keywords: Breast cancer Stem cell CAR-T cell Target Therapy