ovalbumin and Ovarian-Neoplasms

Adoptive cellular therapy (ACT) using T-cell receptor (TCR)-engineered lymphocytes holds promise for eradication of disseminated tumors but also an inherent risk of pathologic autoimmunity if targeted antigens or antigenic mimics are expressed by normal tissues. We evaluated whether modulating TCR affinity could allow CD8

Topics: Allergens; Animals; Antigens, Neoplasm; Autoantigens; CD8-Positive T-Lymphocytes; Cell Line; Diabetes Mellitus, Type 1; Female; Immunotherapy, Adoptive; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Ovarian Neoplasms; Receptors, Antigen, T-Cell

Topics: Female; Formaldehyde; Graphite; Humans; Nanostructures; Ovalbumin; Ovarian Neoplasms; Oxidation-Reduction; Phenol; Phenols; Polymers; Polysaccharides; Porosity; Serum; Serum Albumin

Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8

Topics: Animals; Autoimmunity; CD8-Positive T-Lymphocytes; Female; Homeodomain Proteins; Immunotherapy, Adoptive; Interleukin-2; Male; Mice, Mutant Strains; Mice, Transgenic; Ovalbumin; Ovarian Neoplasms; Peptide Fragments; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta

Topics: Adenylate Cyclase Toxin; Adjuvants, Immunologic; Animals; Antigens, Neoplasm; Cancer Vaccines; Disease Models, Animal; DNA-Binding Proteins; Drug Carriers; Female; Immunologic Memory; Injections, Intradermal; Melanoma; Mice, Inbred C57BL; Neoplasm Proteins; Oncogene Proteins, Viral; Ovalbumin; Ovarian Neoplasms; Papillomavirus E7 Proteins; Papillomavirus Infections; Papillomavirus Vaccines; T-Lymphocytes; Treatment Outcome; Uterine Cervical Neoplasms; Vaccines, Synthetic

Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages, and is associated with a high relapse rate. Patients in remission are ideal candidates for immunotherapy aimed at cure or prolonging disease-free periods. However, immunosuppressive pathways in the tumor microenvironment are obstacles to durable anti-tumor immunity. In a metastatic syngeneic mouse model of EOC, immunosuppressive macrophages and myeloid-derived suppressor cells (MDSCs) accumulate in the local tumor environment. In addition, resident peritoneal macrophages from non-tumor-bearing mice were highly immunosuppressive, abrogating stimulated T cell proliferation in a cell contact-dependent manner. Immunization with microparticles containing TLR9 and NOD-2 ligands (MIS416) significantly prolonged survival in tumor-bearing mice. The strategy of MIS416 immunization followed by anti-CD11b administration further delayed tumor progression, thereby establishing the proof of principle that myeloid depletion can enhance vaccine efficacy. In patients with advanced EOC, ascites analysis showed substantial heterogeneity in the relative proportions of myeloid subsets and their immunosuppressive properties. Together, these findings point to immunosuppressive myeloid cells in the EOC microenvironment as targets to enhance vaccination. Further studies of myeloid cell accumulation and functional phenotypes in the EOC microenvironment may identify patients who are likely to benefit from vaccination combined with approaches that deplete tumor-associated myeloid cells.

Topics: Adoptive Transfer; Animals; Antibodies, Monoclonal; Ascites; Cancer Vaccines; Carcinoma, Ovarian Epithelial; CD11b Antigen; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Disease Progression; Female; Humans; Ligands; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Macrophages; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Cells; Neoplasms, Glandular and Epithelial; Nod2 Signaling Adaptor Protein; Ovalbumin; Ovarian Neoplasms; T-Lymphocytes; Time Factors; Toll-Like Receptor 9; Tumor Escape; Tumor Microenvironment; Vaccination

We hypothesized that ovarian tumors without oviductal involvement would not express the oviductal protein ovalbumin, the major protein found in the magnum of the hen's oviduct.. On the basis of gross visual examination, tissues samples were removed from hens determined to have ovarian tumors and were processed, embedded in paraffin, sectioned, mounted on glass slides, and stained with hematoxylin and eosin. Ovarian tumors and other peritoneal lesions were evaluated histologically. Paraffin sections of ovarian and oviductal tissue were deparaffinized and evaluated for the protein expression of ovalbumin, proliferating cell nuclear antigen (PCNA), and progesterone receptor (PR).. Hens with ovarian adenocarcinoma without (n = 10) or with (n = 6) oviductal involvement were positive for ovalbumin in the ovary. Ovary sections from normal hens (n = 9) were negative, and oviductal sections from normal hens (n = 3) were positive for ovalbumin. Expression of PCNA protein was abundant in all ovarian tumors (16 of 16). Oviductal epithelial cells strongly expressed PCNA protein. Expression of PR was observed in 9 of 14 ovarian tumors.. The presence of ovalbumin in ovarian tumors in the absence of any oviductal involvement suggests that ovarian tumors dedifferentiate during the disease process and thereby resemble serous-type ovarian tumors in women.

Topics: Adenocarcinoma; Animals; Chickens; Cystadenocarcinoma, Serous; Disease Models, Animal; Female; Humans; Ovalbumin; Ovarian Neoplasms; Oviducts; Paraffin Embedding; Proliferating Cell Nuclear Antigen; Receptors, Progesterone