Clinical Course of Ovarian Cancer Patients Under Repeated Stimulation of HAMA Using MAb OC125 and B43.13

Baüm, Richard; Noujaim, A.A.; Nanci, A.; Moebus, Volker; Hertel, A.; Niesen, A.; Donnerstag, B.; Sykes, T. R.; Boniface, G. R.; G, Hör

doi:10.1089/hyb.1993.12.583

Cited by 37 publications

(14 citation statements)

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“…A retrospective analysis of results trials designed to test the use of B43.13 as an imaging agent suggested increased survival in patients developing a human anti-mouse antibody (HAMA) response [157]. Repeated administration of the anti-CA125 antibodies results in increased anti-tumor T cell responses and the generation of anti-idiotypic antibodies [158-165]. These positive results led to the testing of Oregovomab in larger clinical trials in ovarian cancer patients [166,167].…”

Section: Biological Role Of Muc16mentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Biological Role Of Muc16mentioning

confidence: 99%

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

et al. 2014

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“…13 complexes, MAb-B43.13 also activates the idiotypic network (17) . Although robust immune responses including HAMA and Ab 2 responses were frequently observed, these were not associated with limiting toxicities related to hypersensitivity (12)(13)(14) .…”

mentioning

confidence: 97%

A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer

Ehlen¹,

Hoskins²,

Miller³

et al. 2005

Int J Gynecol Cancer

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This prospective, open-label, pilot phase 2 study examined the clinical and immunologic effects of oregovomab (OvaRex) in heavily pretreated patients with recurrent ovarian cancer (OC). Thirteen women were administered intravenous oregovomab (2 mg) at weeks 0, 2, 4, 8, and 12, followed by quarterly doses for up to 2 years or disease progression. Concomitant chemotherapy was not permitted. Eligibility criteria included recurrence after one or more platinum-based chemotherapy regimens, CA125 >35 U/mL, evaluable or measurable disease. Tumor burden was evaluated by physical or radiologic methods pretreatment, weeks 12, 24, and every 24 weeks thereafter. Immune responses, including antibodies and T cells to oregovomab and CA125, were demonstrated in over half the patients. Stabilization of disease and survival >2 years was observed in 3 of 13 patients and coincided with robust immune responses. Shrinkage of marker lesions was not observed; however, four patients showed decreases in CA125 levels. Treatment was well tolerated without serious adverse events or discontinuations due to therapy. This pilot study supports immunologic activity and safety of oregovomab in recurrent OC. Further study of this agent in the consolidation and adjuvant setting is ongoing to establish its clinical utility.

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“…(Molthoff et al 1997). Studies using single or repetitive injections of various (mostly murine) mAbs for diagnostic as well as for therapeutic purposes (in doses comparable to those which have been administered in this pilot study) have shown that these are safe and well tolerated (Baselga et al 1996;Goodman et al 1993;Baum et al 1993).…”

Section: Discussionmentioning

confidence: 80%

“…A major obstacle in the application of murine mAbs is their immunogenicity, which may result in the generation of immune complexes, increased blood clearance, and less effective tumor targeting (Baum et al 1993). Murine MOv18 induced HAMA in the majority of patients ( Crippa et al 1995).…”

Section: Discussionmentioning

confidence: 99%