ABSTRACT
Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body's immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/therapy , Cell- and Tissue-Based TherapyABSTRACT
In this research, a novel dye-labeled probe (FAM-Probe) based on a nano metal-organic framework (NMOF) functionalized with folate (NMOF-FA) was prepared and applied as a fluorescent sensing platform for the recognition of intracellular microRNA (miRNA-21) in DU145, PC3, and LNCaP cancer cells. The NMOF-FA can be easily assembled with a dye-labeled miR-21 probe (FAM-Probe21), causing an efficient fluorescence quenching of fluorescence of FAM fluorophore. The probe can be specifically catch up by cancerous cells through targeting their folate receptor by folic acid on the FAM-Probe21-NMOF-FA complex. Upon the interaction of the FAM-Probe21-NMOF-FA with complementary miRNA (miR-21), the fluorescence intensity can be recovered, providing a specific system to detect miRNAs in prostate cancer cells. We used the proposed probe for cell-specific intracellular miRNA-21 sensing, following the alteration expression level of miRNA-21 inside living cells. Thus, the FAM-Probe21-NMOF-FA complex can be used as a new miRNA sensing method in biomedicine studies.
ABSTRACT
Chimeric antigen receptor T-cells (CAR-Ts) are known as revolutionary living drugs that have turned the tables of conventional cancer treatments in certain hematologic malignancies such as B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) by achieving US Food and Drug Administration (FDA) approval based on their successful clinical outcomes. However, this type of therapy has not seen the light of victory in the fight against solid tumors because of various restricting caveats including heterogeneous tumor antigen expression and the immunosuppressive tumor microenvironments (TME) that negatively affect the tumor-site accessibility, infiltration, stimulation, activation, and persistence of CAR-Ts. In this review, we explore strategic twists including boosting vaccines and designing implementations that can support CAR-T expansion, proliferation, and tumoricidal capacity. We also step further by underscoring novel strategies for triggering endogenous antitumor responses and overcoming the limitation of poor CAR-T tumor-tissue infiltration and the lack of definitive tumor-specific antigens. Ultimately, we highlight how these approaches can address the mentioned arduous hurdles.
