Immunological Responses to the Tumor-Associated Antigen CA15 in Patients with Advanced Ovarian Cancer Induced by the Murine Monoclonal Anti-idiotype Vaccine ACA125

Wagner, Uwe; Schlebusch, H.; Köhler, Silke; Schmolling, J.; Grünn, U.; Krebs, D.

doi:10.1089/hyb.1997.16.33

Cited by 44 publications

(26 citation statements)

References 10 publications

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“…This antibody functionally mimics the CA125 antigen and induces humoral and cellular CA125-specific immunity (11). In previous studies, the antiidiotypic antibody has been shown to induce immune reactivity against CA125-expressing tumors by induction of specific antianti-idiotypic antibodies (also called Ab3; refs.…”

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confidence: 99%

Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Sabbatini

Dupont

Aghajanian

et al. 2006

Clinical Cancer Research

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Purpose: This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerlyACA125) in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Experimental Design: Eligible patients from the three participating institutions were any stage at diagnosis, had relapsed, and had complete or partial response to additional chemotherapy. Patients were randomized to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four immunizations every 2 weeks and then monthly for two additional immunizations. Planned evaluation included interval physical examinations and laboratory assessments with immune assessment, including HLA typing, human anti-mouse antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain on study until week 10 (the first post-baseline Ab3 determination) to be considered for immunologic assessment. The primary end points were safety and immunogenicity primarily determined by Ab3 response. Results: Forty-two patients received at least one vaccination and were eligible for safety analysis. Thirty-three patients were available for Ab3 analysis (removed for progression of disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most common adverse events were self-limited pain at injection site, myalgia, and fever. No hematologic or nonhematologic toxicity grade >2 related to immunization was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of route of administration (P = 0.6268), dose (P = 0.4602), or cohort (P = 0.4944) was statistically significant in terms of effect on maximum post-baseline Ab3 titer. Human anti-mouse antibody was not detectable at baseline but was present in all patients at week 16 (range, 488-45,000 ng/mL). Conclusions: Immunization with abagovomab is well tolerated and induced robust Ab3 responses at the two doses and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is warranted.

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confidence: 99%

Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Sabbatini

Dupont

Aghajanian

et al. 2006

Clinical Cancer Research

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“…30 OVCA cells express mutated forms of p53 [31][32][33] and/or BRCA-1 34,35 tumor suppressor genes. Ovarian tumor cells also express high levels of the CA-125 [36][37][38] and MUC1 39 TAA. In addition, these tumors express abundant levels of the HER2/neu (c-erB2) and epidermal growth factor receptors.…”

Section: Discussionmentioning

confidence: 99%

Induction of cytotoxic T lymphocytes against ovarian cancer‐initiating cells

Weng

Song

Durfee

et al. 2011

Intl Journal of Cancer

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The majority of patients with stage III/IV ovarian carcinoma that respond initially to standard therapies ultimately undergo relapse due to the survival of small populations of cells with tumor-initiating potential. These ovarian cancer (OVCA)-initiating cells (OCIC) are sometimes called cancer stem cells (CSC) because they express stem cell markers, and can survive conventional therapies such as chemotherapy, which usually target rapidly replicating tumor cells, and give rise to recurrent tumors that are more chemo-resistant and more aggressive. Thus, it would be desirable to develop a therapy that could selectively target OCIC and be used to complement the conventional therapies. In this study, we isolated a subset of OVCA cells with a CD44 1 phenotype in samples from patients with OVCA that possess CSC properties including the formation of spheroids in culture, self-renewal and the ability to be engrafted in immune-compromised mice. We next explored the use of immunotherapy using fusions of dendritic cells and OCIC to specifically target the OCIC subpopulations. Fusion cells (FCs) prepared in this way activated T cells to express elevated levels of IFN-c with enhanced killing of CD44 1 OVCA cells. We envision a combined approach where conventional therapies such as chemotherapy kill the bulk of tumor cells, whereas OCIC-reactive cytotoxic T lymphocytes target the resistant OCIC fraction. A combined therapy such as this may represent a promising approach for the treatment of OVCA.Epithelial ovarian cancer (EOC) is responsible for the majority of gynecologic cancer deaths despite recent advances in adjuvant chemotherapy. Indeed, the majority of patients with Stage III/IV ovarian cancer (OVCA) that respond initially to standard therapies ultimately relapse due to drug-resistant disease refractory to further treatment with chemotherapy.

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“…Interestingly, patients with cytotoxic T-cells (CTLs) against MUC16 had a better clinical prognosis regardless of whether they received therapy, suggesting the importance of MUC16 in ovarian cancer [49]. Other than monoclonal antibodies, studies have also investigated the use of vaccinations such as the ACA125 vaccine, which showed a 3-month improvement in progression free survival in patients with advanced ovarian cancer [50,51]. Similarly, another preclinical study investigating a MUC16 vaccine showed that patients generated an IgG response, however the clinical utility is yet to be determined [52].…”

Section: Anti-muc16 Antibodiesmentioning

confidence: 99%

Targeting MUC16 in Cancer Therapy

Suh¹,

Valle²,

Morris³

2017

Chemotherapy (Los Angel)

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Over the recent decades, there has been a number of studies investigating the role of mucins in the pathogenesis of various cancers such as breast, lung, ovarian, gastrointestinal and pancreatic malignancies. Since then, it has been discovered that mucins play a critical role in tumorigenesis as they can mediate cell proliferation, metastasis and resistance to chemotherapy. Thus, mucins have been explored as a potential therapeutic target as well as a biomarker, as cancer cells often have an aberrant expression of mucins. MUC16 is a glycoprotein coded by one of the 21 mucin genes. CA125, the extracellular domain of MUC16, is a well-established biomarker for ovarian cancer, however there is no in depth literature review on MUC16 as a target for anti-cancer therapy. Thus, this review summarises the existing literature on MUC16, the current therapies targeting on MUC16 and highlights future avenues for targeting mucin-producing cancers.

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Immunological Responses to the Tumor-Associated Antigen CA15 in Patients with Advanced Ovarian Cancer Induced by the Murine Monoclonal Anti-idiotype Vaccine ACA125

Cited by 44 publications

References 10 publications

Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Induction of cytotoxic T lymphocytes against ovarian cancer‐initiating cells

Targeting MUC16 in Cancer Therapy

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