Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3–5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.

/pdf/muc16-ca125-tumor-biomarker-to-cancer-therapy-a-work-in-ajxawaog0k.pdf

MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress

The use to e of tetrafluoropropenes, particularly (HFO-1234) in a variety of applications, including refrigeration equipment, is disclosed. These materials are generally useful as refrigerants for heating and cooling, as blowing agents, as aerosol propellants, as solvent composition, and as fire extinguishing and suppressing agents.

Compositions containing fluorine substituted olefins

Purpose: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) enhances the antitumor activity by redirecting T cells and Fcγ receptor I/III–positive accessory cells to the tumor. This multicenter phase I/II dose-escalating study investigated tolerability and efficacy of i.p. catumaxomab application in ovarian cancer patients with malignant ascites containing epithelial cell adhesion molecule (EpCAM)–positive tumor cells.

Experimental Design: Twenty-three women with recurrent ascites due to pretreated refractory ovarian cancer were treated with four to five i.p. infusions of catumaxomab in doses of 5 to 200 μg within 9 to 13 days.

Results: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 μg for the first through fifth doses. Side effects included transient fever (83%), nausea (61%), and vomiting (57%), mostly CTCAE (Common Terminology Criteria for Adverse Events) grade 1 or 2. A total of 39 grade 3 and 2 grade 4 treatment-related adverse events (AE), 9 of them after the highest dose level (200 μg), were observed in 16 patients. Most AEs were reversible without sequelae. Treatment with catumaxomab resulted in significant and sustained reduction of ascites flow rate. A total of 22/23 patients did not require paracentesis between the last infusion and the end of study at day 37. Tumor cell monitoring revealed a reduction of EpCAM-positive malignant cells in ascites by up to 5 log.

Conclusion: I.p. immunotherapy with catumaxomab prevented the accumulation of ascites and efficiently eliminated tumor cells with an acceptable safety profile. This suggests that catumaxomab is a promising treatment option in ovarian cancer patients with malignant ascites.

https://clincancerres.aacrjournals.org/content/clincanres/13/13/3899.full.pdf

Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study.

The present application relates to anti-PD-L1 antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity.

Anti-PD-L1 antibodies, compositions and articles of manufacture

Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer.

Disclosed are methods and compositions for use in immunotherapy. These methods and compositions are particularly useful for exploiting dendritic cells to present an antigen to a patient, particularly where the patient has a disease associated with the antigen. The invention provides methods for treating a patient having a disease associated with an antigen. The methods according to the invention comprise combining ex vivo an antigen and an antigen-presenting cell binding agent specific for the antigen, and administering the composition to a patient suffering from a disease associated with the antigen, wherein the patient receives a therapeutic benefit.

Therapeutic method and composition utilizing antigen-antibody complexation and presentation by dendritic cells

The invention concerns methods and compositions for initiating and/or enhancing an immune response by contacting a binding reagent with a soluble antigen, wherein the binding reagent-antigen pair generates an immune response to the antigen.

Method and composition for reconforming multi-epitopic antigens to initiate an immune response

The invention is therapeutic methods and compositions that alter the immunogenicity of the host.

Therapeutic compositions that alter the immune response

Disclosed are methods for treating cancer comprising administering a xenotypic antibody and a chemotherapeutic drug to a patient suffering from cancer. Also disclosed is a method for inducing a host immune response in a patient against a multi-epitopic in vivo tumor antigen present in the host serum, which antigen does not elicit an effective host immune response, comprising administering to the patient a chemotherapeutic drug and a composition comprising a binding agent that specifically binds to a first epitope on the antigen and allowing the binding agent to form a binding agent/antigen pair, wherein an effective host immune response is elicited against a second epitope on the antigen.

Combination therapy for treating disease

The invention concerns methods and compositions for stimulating a host's immune response, particularly for the treatment of cancer. The methods and compositions according to the invention use binding agents such as antibodies to generate an immune response to a predetermined soluble antigen. In accordance with the invention, the binding agent-soluble antigen complex alters the immunogenic condition of the host by generating new immunogens that are recognizable by the immune system. This leads to a humoral and/or cellular immune response.

Therapeutic compositions that produce an immune response by altering the antigen

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