Abstract
Triple-negative breast cancer (TNBC) is characterized by extensive tumor heterogeneity at both the pathologic and molecular levels, particularly accelerated aggressiveness, and terrible metastasis. It is responsible for the increased mortality of breast cancer patients. Due to the negative expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2, the progress of targeted therapy has been hindered. Higher immune response in TNBCs than for other breast cancer types makes immunotherapy suitable for TNBC therapy. At present, promising treatments in immunotherapy of TNBC include immune checkpoints (ICs) blockade therapy, adoptive T-cell immunotherapy, and tumor vaccine immunotherapy. In addition, nanomedicines exhibit great potential in cancer therapy through the enhanced permeability and retention (EPR) effect. Immunotherapy-involved combination therapy may exert synergistic effects by combining with other treatments, such as traditional chemotherapy and new treatments, including photodynamic therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT). This review focuses on introducing the principles and latest development as well as progress in using nanocarriers as drug-delivery systems for the immunotherapy of TNBC.
Highlights
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China; Department of Molecular Chemistry and Materials Science, Weizmann Institute of Science, The authors contribute to this work
Based on the asynchronous expression of the above-mentioned receptors, this study shows that siCD155-mediated knockdown of CD155 by P/PEALsiCD155 can achieve spatiotemporal targeting of surface receptors and intracellular mRNA, making the antitumor effect take place in favorable periods, i.e., promoted CD155-mediated immune surveillance in the early stage and inhibited CD155-mediated immune evasion in the later stage
Progress has been made in new treatments, including CAR-T and tumor immunization vaccines
Summary
The adoptive T-cell immunotherapy starts with isolating T cells, which are afterwards genetically modified to express CRA, followed by proliferation, are reinjected to patients. To develop an effective CARs therapy for TNBCs, it is necessary to select a desired tumor cell-surface antigen, which can be express stably in most tumor cells, and has high tumor specificity [47]. For this purpose, Song et al [48] designed a new folate receptor α (FRα)-specific CAR-T, which was composed of MOv19 scFv and CD8a hinge in extracellular region, and of CD27 costimulatory domain and CD3ζ signaling domain in the intracellular region. EGFR-specific CAR-T with THZ1, a CDK7 inhibitor, which together demonstrated a good effect on TNBCs proliferation, tumor metastasis and suppressed immune resistance in mice. Stuber et al [51] combined ROR1-specific CAR-T cells to SD-208, a TGF-β inhibitor, to weaken the immunosuppressive effects in therapy
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