Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.
Antigens, Neoplasm/chemistry* ; Biomarkers, Tumor/metabolism* ; Glycosylation ; Hematologic Neoplasms/drug therapy* ; Humans ; Immunotherapy, Adoptive/methods* ; Male ; Neoplasm Recurrence, Local/metabolism* ; Receptors, Chimeric Antigen ; T-Lymphocytes ; United States

Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.
Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; chemistry ; therapeutic use ; Carbonic Anhydrase IX ; Carbonic Anhydrase Inhibitors ; chemistry ; therapeutic use ; Carbonic Anhydrases ; metabolism ; Humans ; Neoplasms ; drug therapy ; enzymology

Animals ; Antigens, Neoplasm ; chemistry ; immunology ; Cancer Vaccines ; chemistry ; therapeutic use ; Cell Line, Tumor ; CpG Islands ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; metabolism ; Humans ; In Vitro Techniques ; Lactic Acid ; chemistry ; Leukemia ; immunology ; therapy ; Lymphocytes ; cytology ; immunology ; Nanoparticles ; chemistry ; Peptides ; chemistry ; immunology ; therapeutic use ; Polyglycolic Acid ; chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer ; WT1 Proteins ; chemistry ; immunology

No abstract available.
Adult ; Antibiotics, Antineoplastic/administration & dosage ; Antigens, CD34/metabolism ; Antigens, CD56/metabolism ; Antigens, Neoplasm/metabolism ; Carcinoma, Hepatocellular/metabolism/*pathology/therapy ; Cell Adhesion Molecules/metabolism ; Chemoembolization, Therapeutic ; Doxorubicin/administration & dosage ; Ethiodized Oil/chemistry ; Hepatitis B/diagnosis ; Humans ; Liver Cirrhosis/diagnosis ; Liver Neoplasms/*pathology/therapy ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed

Recent studies reported that thymoquinone (TQ), a component derived from the medicinal spice Nigella sativa (also called black cumin), exhibited inhibitory effects on cell proliferation of many cancer cell lines. This study was performed to investigate the anti-metastatic effect of thymoquinone on the pancreatic cancer in vitro and in vivo. The results showed that thymoquinone suppressed the migration and invasion of Panc-1 cells in a does-dependent manner. To investigate the possible mechanisms involved in these events, Western blotting analysis was performed, and found that thymoquinone significantly down-regulates NF-kappaB and MMP-9 in Panc-1 cells. In addition, metastatic model simulating human pancreatic cancer was established by orthotropic implantation of histologically intact pancreatic tumor tissue into the pancreatic wall of nude mice. And administration of thymoquinone significantly reduced tumor metastasis compared to untreated control. Furthermore, the expression of NF-kappaB and MMP-9 in tumor tissues was also suppressed after treatment with thymoquinone. Taken together, the results indicate that thymoquinone exerts anti-metastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-kappaB and its regulated molecules such as MMP-9 protein. Consequently, these results provide important insights into thymoquinone as an antimetastatic agent for the treatment of human pancreatic cancer.
Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents, Phytogenic ; administration & dosage ; isolation & purification ; pharmacology ; Benzoquinones ; administration & dosage ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Female ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; NF-kappa B ; metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; Nigella sativa ; chemistry ; Pancreatic Neoplasms ; metabolism ; pathology ; Plants, Medicinal ; chemistry

More and more evidences support the cancer stem cell (CSC) hypothesis which postulates that CSCs are responsible for tumor initiation metastasis recurrence and resistance to treatments. Therefore they are the targets of antitumor therapy. Sorting CSCs using specific surface markers is the premise of investigating their biological behaviors. Recently CD133 has been used extensively as a marker for the identification of stem cells from normal and cancerous tissues. Moreover CD133- positive (CD133+) tumor cells associate with the self-renewal differentiation potentials signal pathway drug-resistance recurrence and prognosis of tumors. Therefore CD133+ cells could be potential targets of antitumor therapy in the future.
AC133 Antigen ; Animals ; Antigens, CD ; chemistry ; metabolism ; Biomarkers, Tumor ; metabolism ; Cell Separation ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Glycoproteins ; chemistry ; metabolism ; Humans ; Neoplasms ; drug therapy ; pathology ; therapy ; Neoplastic Stem Cells ; metabolism ; Peptides ; chemistry ; metabolism ; Signal Transduction ; physiology ; Stem Cell Transplantation

Adult ; Antigens, Neoplasm ; analysis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Melanoma ; cerebrospinal fluid ; metabolism ; pathology ; Melanoma-Specific Antigens ; Melanosis ; cerebrospinal fluid ; metabolism ; pathology ; Meningeal Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Meninges ; chemistry ; pathology ; Neoplasm Proteins ; analysis ; S100 Proteins ; analysis

OBJECTIVETo evaluate the anti-angiogenic activity of peptide 21 obtained by modification of tumstatin, and its inhibitory effect on the growth and metastasis of human ovarian cancer transplanted in nude mice.

METHODSThe peptide 21 was purified by affinity chromatography. Human ovarian cancer SKOV3 cells were inoculated in nude mice and the transplanted tumor was treated with the peptide 21 to observe the tumor growth and metastasis. The microvessel density (MVD) and immunohistochemical staining index of PCNA, VEGF and MMP-2 and TIMP-2 were performed to assess the inhibitory effect of the peptide 21.

RESULTSIn the nude mice at 21 days after peptide 21 treatment, the inhibition rate of tumor growth was 53.17%, the tumor microvessel density was significantly reduced (P <0.05), the expression of PCNA, VEGF and MMP-2 were significantly lower (P <0.01), and TIMP-2 expression was significantly higher (P <0.01) in comparison with that of control group.

CONCLUSIONThe peptide 21 generated in this study has a significant anti-angiogenetic activity, showing significant inhibitory effect on the growth of human ovarian cancer transplanted in nude mice. The mechanism of its inhibitory action on ovarian cancer growth may be mediated by reduction of neovascularization and reduction of expression of angiogenetic factors.

Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; chemistry ; pharmacology ; Autoantigens ; chemistry ; pharmacology ; Cell Line, Tumor ; Collagen Type IV ; chemistry ; pharmacology ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; pathology ; prevention & control ; Ovarian Neoplasms ; metabolism ; pathology ; Peptides ; chemistry ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Recombinant Proteins ; chemistry ; pharmacology ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

KM-HN-1 is a C-terminal coiled-coil domain containing protein previously referred to as image clone MGC33607. This protein has been previously identified as a cancer/testis antigen and reported as nuclear and chromatin localizing protein. We raised polyclonal antisera with the GST fusion protein and identified them as a 105 kDa protein. Motif analysis showed that this protein harbors the leucine zipper motif in internal 1/3 region and the coiled-coil domain in the C-terminal region. Using the full length and various deletion mutants, we determined the motif that governs the subcellular localization of KM-HN-1. Immunofluorescence staining of the endogenous KM-HN-1 and various kinds of GFP-tagged KM-HN-1 revealed that KM-HN-1 localizes to the centrosomes as well as nucleus. The centrosomal localization-determining region of this protein is C-terminal coiled-coil domain in which the leucine zipper motif and the nuclear export signal (NES) harbor.
Amino Acid Motifs/physiology ; Amino Acid Sequence ; Antigens, Neoplasm/chemistry/*metabolism ; Cells, Cultured ; Centrosome/*metabolism ; Fluorescent Antibody Technique ; Humans ; Leucine Zippers/*physiology ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/chemistry/*metabolism ; Protein Conformation ; Protein Structure, Tertiary ; Sequence Analysis, Protein

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.
S100 Proteins/chemistry ; Neoplasm Metastasis ; Muscle, Smooth/pathology ; Middle Aged ; Metaplasia ; Keratins/metabolism ; Immunohistochemistry ; Humans ; Female ; Cell Differentiation ; Carcinoma/*complications/metabolism/pathology ; CA-15-3 Antigen/metabolism ; Breast Neoplasms/complications/metabolism/*pathology ; Antigens, CD34/biosynthesis ; Actins/metabolism