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Recent Advances of Nanotechnologies for Cancer Immunotherapy Treatment
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Immune checkpoints are crucial for maintaining immune homeostasis and preventing autoimmunity as they are regulators of immune system. However, increasing research has identified that in various types of cancer, the intrinsic mechanisms of immune checkpoint are overactivated resulting in escaping immune surveillance on tumor cells. Owning to the overactivation of immune checkpoint, a majority of effector T cells would differentiate into exhausted T cells at late stage of diseases. The inhibitory receptors are normally overexpressed on exhausted T cells, and effector cytokines’ secretion is also decreased [18]. Thus, it is vital to recover T cells’ effector function and reverse immunosuppressive tumor microenvironment to improve potent antitumor immunity. In many preclinical trials, it has been demonstrated that immune checkpoint inhibitors could release inhibitory mechanisms of T-cell-mediated immunity and promote CTL responses [19]. Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis, indoleamine 2,3-dioxygenase (IDO), cluster of differentiation 47 (CD47), cluster of differentiation 40 (CD40), and 4-1BB (CD137), are at the forefront of immunotherapy for a variety of cancers. The expression patterns, intrinsic signaling pathways, and mechanisms of these immune checkpoint inhibitors are quite different from each other despite of some commonalities. The two major kinds of antibodies, CTLA-4 and PD-1/PD-L1 axis, have exhibited significant clinical successes and provided great potential in cancer immunotherapy [20,21].
Two-Dimensional Nanomaterials for Drug Delivery in Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Zahra Mohammadpour, Seyed Morteza Naghib
There are some immunosuppressive pathways, the result of which is escaping tumours from being recognised by the immune system. The antibodies that block programmed cell death protein 1 (PD1) and its ligand (PDL1) can restore the immune responsivity towards tumours. The therapeutic strategy is called checkpoint blockade immunotherapy (CBI). However, it has been reported that radical therapy as an immunostimulatory treatment is also immunogenic. In radical therapy, the tumour cells are killed by ROSs that are generated either by an external stimulus such as ultrasonic waves (sonodynamic therapy) and photons (photodynamic therapy) or by endogenous tumour microenvironments (chemodynamic therapy). The latter proceeds through metal ion-mediated decomposition of hydrogen peroxide and ROS generation. Lin’s research team showed that a combination of CBI and chemo/photodynamic therapy could synergistically restore the immune responsivity towards tumours (Ni et al. 2019; Ni et al. 2020a; Ni et al. 2020b). To this end, they employed Cu2+ containing MOF nanosheets (Cu-TBP) (Ni et al. 2019). Diverse chemical composition and porous structure have made MOFs useful for loading different cargos. Besides, the inclusion of redox-active metal ions and radiosensitisers as ligands in the structure of MOFs provides efficient means for conducting chemo and photodynamic therapies. Cu-TBP MOFs were efficiently delivered into the cells. The released Cu2+ metal cations and TBP photosensitisers took part in ROS production through chemo and photodynamic pathways and regressed the local tumour. The Cu-TBP was injected inside the tumour, and the anti-PD-L1 antibody was given to the animal model every three days. Not only the primary tumours were eradicated but also the distant tumours of one-third of mice disappeared due to the anti-tumour immunity induced by the synergistic therapy. The treated mice were rechallenged with new tumour cells after a month. Interestingly, they remained tumour free due to the induced immune memory. The same group employed nanoscaled MOFs (Hf-DBP) to reverse the immunosuppression of tumours by co-delivery of imiquimod and αCD47 (Ni et al. 2020a). Imiquimod was loaded inside the pores of the MOF, and αCD47 adsorbed on its surface. Imiquimod is a hydrophobic drug molecule that activates the toll-like receptor-7 (TLR-7) pathway. αCD47 is an antibody that blocks the CD47 checkpoint signalling molecule on the surface of tumour cells. The TLR-7 pathway activated inflammatory macrophages (M1), which subsequently took part in cytokine secretion, phagocytosis, and antigen presentation to naïve T cells inside the lymph nodes. The activated T cells then invaded the tumour cells, of which the PDL1 proteins were blocked by αPDL1. The T cells recognised and killed the cancer cells (Figure 2.4). This way the macrophage therapy was synergised with CBI, which eradicated both the primary and distal tumours of the animal models.
Effective blocking of neuropilin-1activity using oligoclonal nanobodies targeting different epitopes
Published in Preparative Biochemistry & Biotechnology, 2023
Elmira Karami, Maryam Mesbahi Moghaddam, Mahdi Behdani, Fatemeh Kazemi-Lomedasht
ELISA was used to evaluate the specificity and binding ability of nanobodies to immobilized NRP-1 antigen. In this test, 1 µg/mL of different antigens (NRP-1, VEGF (vascular endothelial growth factor), VEGFR2 (vascular endothelial growth factor receptor 2), EpCAM (epithelial cell adhesion molecule), PD-1 (programmed cell death protein 1), PD-L1 (programmed death-ligand 1), CTLA-4 (cytotoxic T-lymphocyte–associated antigen 4), LIV-1 (and zinc transporter protein), and BSA were coated overnight at 4 °C. The next day after blocking (skim milk 2%, 2 h) and washing the wells, 1 µg/mL of nanobodies (oligoclonal or monoclonal) were added to the wells and incubated at RT for 1 h. Finally, the wells were washed and incubated with TMB, and OD was measured at 450 nm.[36,37]