China
Africa
Explore chapters and articles related to this topic
Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sidharth Mahapatra, Naveenkumar Perumall
Malignant cells have the capacity to evade immunologic surveillance through the expression of unique cell surface markers making them immune resistant. One of these markers that is highly expressed in a variety of tumor types, CD47, activates the signal regulatory protein alpha (SIRPoc) on myeloid cells, which in turn, protects the malignant cells from phagocytosis by macrophages [108]. Using the anti-CD47 antibody, Hu5F9-G4, authors demonstrated not only elevated tumor cell phagocytosis and growth inhibition but also an inhibition of neuroaxis spread in xenograft models of high MYC-expressing medulloblastoma [109]. Similarly, B7-H3 (CD276), which is an immune checkpoint member of the B7 family, plays a role in the functional inhibition of T-cells and is overexpressed in a variety of solid tumors, often correlated with poor prognosis [110]. A variety of clinical-translational advances have been made in B7-H3 targeting for cancer therapy, including blocking antibodies, bispecific antibodies, small molecule inhibitors, and chimeric antigen receptor T-cell (CAR T-cell) therapy [110, 111]. In an MYC-amplified medulloblastoma xenograft model, B7-H3 CAR T-cell infusion into the posterior fossa led to dramatic reduction in tumor burden and prolonged survival [111]. Finally, an emerging and provocative new approach to high-risk medulloblastoma treatment is exploiting telomerase targeting. By incorporating a telomerase substrate, 6-thio-dG, into the telomeres of tumor cells, authors demonstrated a dose-dependent inhibition of MB cell growth in vitro with reduced tumor sphere formation and elevated apoptosis [112].
Immunotherapy
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Sowmiya Renjith, Sathya Chandran
It is now evident that tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Because many of the immune checkpoints are triggered by ligand-receptor interactions, they can be actively blocked by antibodies or manipulated by recombinant forms of ligands or receptors. Ipilimumab, a mAb against CTLA-4 that has acquired FDA approval for metastatic melanoma, is presently being evaluated in clinical trials along with cetuximab and intensity-modulated radiation therapy (IMRT) in individuals with advanced HNSCC (NCT01860430 and NCT01935921). A phase 1, open-label, dose escalation study of MGA271 (enoblituzumab, a humanized mAb against CD276 [B7-H3] in combination with ipilimumab in patients with B7-H3–expressing HNSCC and other solid tumors) is also proceeding (NCT02381314). Tremelimumab is another anti-CTLA4 antibody presently being assessed in clinical trials.
The Immunomodulatory Features of Mesenchymal Stromal Cells Derived from Wharton’s Jelly, Amniotic Membrane, and Chorionic Villi In Vitro and In Vivo Data
Published in Ornella Parolini, Antonietta Silini, Placenta, 2016
Marta Magatti, Mohamed H. Abumaree, Antonietta R. Silini, Rita Anzalone, Salvatore Saieva, Eleonora Russo, Maria Elena Trapani, Giampiero La Rocca, Ornella Parolini
Another costimulatory molecule that belongs to the B7 family is the B7-H3 (CD276) protein. Flow cytometry and immunohistochemical analyses have shown that it is expressed by hWJMSCs (La Rocca et al. 2013b), hAECs (Petroff and Perchellet 2010), and hCVMSCs (Abumaree et al. 2013b). In addition, the molecule has been shown to be expressed not only in naive hWJMSCs but also in their in vitro–differentiated (toward osteogenic, adipogenic, and chondrogenic lineages) counterparts, a characteristic described above also for HLA-G, -E, and -F (La Rocca et al. 2013b). B7-H3 is an important T cell–immunosuppressive molecule that has been reported to consistently downregulate human T cell cytokine production and proliferation (Leitner et al. 2009). Finally, in contrast to PD-L1, PD-L2, and B7-H3, B7-H2 (CD275 or ICOS-L), the ligand for ICOS and provider of positive costimulatory effects promoting T cell activation, differentiation, and effector responses (Coyle et al. 2000; Petroff and Perchellet 2010; Yoshinaga et al. 1999), is not expressed by hAECs (Petroff and Perchellet 2010), hAMSCs (Kronsteiner et al. 2011b), and hCVMSCs (Abumaree et al. 2013b).
B7-H3 targeted antibody-based immunotherapy of malignant diseases
Published in Expert Opinion on Biological Therapy, 2021
Theodoros Michelakos, Filippos Kontos, Omar Barakat, Luke Maggs, Joseph H. Schwab, Cristina R. Ferrone, Soldano Ferrone
B7-H3 (also known as CD276), is a type I transmembrane protein belonging to the B7 immune co-stimulatory and co-inhibitory family. It maintains its structure, most of its aminoacid sequence and its functional properties through phylogenetic evolution [14]. Its exact biological function(s) remain(s) unclear, however, it seems to act as both a co-stimulatory and/or a co-inhibitory molecule depending on the involved immune cells and on the microenvironment conditions [15,16]. In humans it is encoded by chromosome 15q24 and consists of an extracellular domain, a transmembrane domain and a short intracellular tail with no known signaling motif. B7-H3 exists in two isoforms: 2IgB7-H3 which comprises a single pair of immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like extracellular domains, and 4IgB7-H3 (protein moiety ~45-66 kDa, glycosylated isoform ~100 kDa [17]) which comprises two identical pairs of IgV-like and IgC-like extracellular domains due to exon duplication [18–20]. The latter is the predominant isoform on human cells (Figure 1). An isoform present in serum has also been described [21]. B7-H3 is expressed in many normal and malignant tissues at the mRNA level, however it is subject to post-transcriptional regulation by microRNAs, leading to limited expression in normal tissues at the protein level [22,23]. Therefore, mRNA expression cannot be used as a marker of B7-H3 expression at the protein level.
Proteomic approaches to assist in diagnosis and prognosis of oral cancer
Published in Expert Review of Proteomics, 2021
Jamile De Oliveira Sá, Luciana Daniele Trino, Ana Karina Oliveira, Ariane Fidelis Busso Lopes, Daniela Campos Granato, Ana Gabriela Costa Normando, Erison Santana Santos, Leandro Xavier Neves, Carolina Moretto Carnielli, Adriana Franco Paes Leme
Overexpression of DPAGT1 in human OSCC tumor specimens, compared to adjacent epithelia, was associated with aberrant activation of the canonical Wnt signaling pathway that has been established as a contributor to the development and progression of many human cancers [110–112]. Moreover, using a sialylation probe to enrich glycoproteins and LC-MS/MS analysis, Chen et al. [113] identified exclusive glycoproteins in the Ca9-22 compared to SG cell line, from which B7-H3 glycoprotein was the most significant. Through MS site-specific glycoprofiling approach, the authors identified lower levels of sialylation and higher fucosylation levels in the OSCC cell line. The study also revealed that B7-H3 knockdown suppressed the tumor cell proliferation and enhanced tumor growth after B7-H3 restoration. Interestingly, in IHC analysis of 72 FFPE samples from well-differentiated OSCC patients, the glycoprotein B7-H3 is observed in higher levels and was associated with a poor prognosis. The B7-H3, also called CD276, is involved in the regulation of T-cell-mediated immune response and the regulation of non-immunological pathways, and it is a promising therapeutic target in cancer treatment [114].
B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells
Published in OncoImmunology, 2020
Huimin Lu, Tongguo Shi, Mingyuan Wang, Xiaomi Li, Yanzheng Gu, Xueguang Zhang, Guangbo Zhang, Weichang Chen
As an important member of the B7 superfamily, B7-H3 (also known as CD276) is a type I membrane protein.22 The extracellular domain of B7-H3 in mice contains one IgV domain and one IgC domain (2IgB7-H3 isoform), and two identical pairs of domains are found in human B7-H3 (4IgB7-H3 isoform).23,24 B7-H3 mRNA is broadly expressed by nonlymphoid and lymphoid organs, while the B7-H3 protein is expressed on immune cells, including dendritic cells (DCs), monocytes, natural killer (NK) cells, B cells, and T cells.25 B7-H3 was shown to modulate the biological functions of immune cells, including macrophages,22 NK cells,26 CD4+ T cells,23 and CD8+ T cells,23,27 and exerted a dual role in regulating the innate and adaptive immune responses.22 However, no reports in the literature have addressed the potential contribution of B7-H3 to the regulation of γδ T cells.