The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR

Pfisterer, Jacobus; Bois, Andreas du; Sehouli, Jalid; Loibl, Sibylle; Reinartz, Silke; Reuß, Alexander; Canzler, Ulrich; Belau, A.; Jackisch, Christian; Kimmig, Rainer; Wollschlaeger, K.; Heilmann, V.; Hilpert, Felix

doi:10.1093/annonc/mdl357

Cited by 64 publications

(49 citation statements)

References 24 publications

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“…Interestingly, a correlation between specific humoral response to abagovomab and patients' survival has also emerged, so that randomized, controlled studies are now warranted to possibly prove clinical benefit (Reinartz et al, 2004). However, it seems fair to underline that other subsequent clinical trials on recurrent ovarian cancer (Pfisterer et al, 2006) and on a miscellanea of gynecologic/peritoneal primary tumors (Sabbatini et al, 2006) seem to confirm the encouraging results above. Moreover, pre-clinical data suggest that the integration of IL-6 within the abagovomab formulation -as a fusion protein -might improve efficacy by eliciting even more robust, CA125-specific humoral responses (Reinartz et al, 2003).…”

Section: Ovarian Cancermentioning

confidence: 98%

Anti-idiotype antibodies in cancer treatment

et al. 2007

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As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways over the last three decades, depending on the actual human tumor cell target. It all started with passive, monoclonal, anti-Id antibody treatment of B-cell lymphoma, a setting in which results were tantalizing, but logistics unsustainable. It then moved toward the development of anti-Id vaccines for the treatment of the same tumors, a setting in which we have recently provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting the antigenic mimicry of some Ids with Idunrelated, tumor-associated antigens for the immunotherapy of a number of solid tumors, a setting in which clinical results are still far from being consolidated. All in all, over the years Id-based immunotherapy has paved the way for a number of seminal therapeutic improvements for cancer patients, including the development of most if not all Id-unrelated monoclonal antibodies that have recently revolutionized the field.

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Section: Ovarian Cancermentioning

confidence: 98%

Anti-idiotype antibodies in cancer treatment

et al. 2007

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“…Recently, Pfisterer et al (62) performed a phase I trial in 36 recurrent ovarian cancer patients on the effect of subcutaneous administration of ACA 125 which was prematurely terminated due to patient withdrawal or disease progression. However, sc administration of ACA 125 did seem safe and was well-tolerated also in highly frequent dosage schedules (62).…”

Section: Clinical Trialsmentioning

confidence: 99%

“…(27,58), one study administered through ip, iv and intradermal routes (58) and one study only used sc route of Mabs administration (62). The median number of patients included was 29 (range 3-447).…”

Section: Clinical Trialsmentioning

confidence: 99%

The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

Massuger¹,

Boerman²,

Thomas³

et al. 2008

Int J Oncol

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Abstract.The prognosis for patients with ovarian cancer is still poor and more effective therapeutic modalities are needed. (Radio)immunotherapy using monoclonal antibodies (Mabs) could be one of these approaches. Here, we review the status of (radio)immunotherapy using Mabs for the treatment of ovarian cancer. The Pubmed database was searched for clinical trials investigating the effect of (radio)immunotherapy in ovarian cancer published until October 1, 2007. Keywords for the search were: ovarian cancer, monoclonal antibodies, CA 125, gp38, HER2, HMFG, MUC1, TAG 72 and VEGF. A total of 44 trials on immunotherapy with unconjugated Mabs, Mab vaccination and (radio)immunotherapy directed towards the antigens CA 125, gp38, HER2, MUC1, TAG 72 or VEGF in patients with ovarian cancer were found, reviewed and discussed. Out of these trials, 23 studied immunotherapy with unconjugated Mabs, 5 vaccination with Mabs and 16 trials studied (radio)immunotherapy. The lack of large randomized prospective trials with Mabs directed to tumor-associated antigens expressed on ovarian cancer cells preclude any firm conclusion on the potential of Mabs use in the treatment of ovarian cancer. Oregovomab, directed against CA 125, and bevacizumab, targeting VEGF, are two unconjugated Mabs closest to clinical introduction for the treatment of ovarian cancer. Vaccination with Mab ACA 125 seems promising but these findings need to be confirmed in controlled randomized trials. Sole RIT should be investigated with the appropriate radionuclide and a Mab with high affinity for the specific tumor-associated antigen in the appropriate patient group to determine whether it may have a therapeutic effect. Additionally, appending (radio)immunotherapy with anti-TAG 72 or anti-MUC1 to other treatment strategies such as chemotherapy could also be a strategy worthwhile investigating. The potential of Mabs to complement current treatment paradigms, is encouraging and may bring a significant improvement to the overall therapeutic outcomes currently being achieved in ovarian cancer. IntroductionOvarian cancer is the fourth leading cause of cancer-related death in women, and accounts for the highest mortality rate of all gynecological malignancies (1). Its poor prognosis is mainly the result of the clinically occult nature of this disease. The peritoneal cavity in which the ovaries are localized provides a perfect environment for undisturbed subclinical growth. Furthermore, early detection is difficult because of the general asymptomatic presentation of the disease (2). In the majority (68%) of the patients, ovarian cancer is diagnosed with at least extensive abdominal spread (3). Standard treatment for advanced stage ovarian cancer is tumor debulking surgery and adjuvant chemotherapy. Although most ovarian cancers are sensitive to platinumbased chemotherapy, the prognosis remains poor. The 5-year INTERNATIONAL JOURNAL OF ONCOLOGY 32: 1145-1157 The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (Review) Abbreviations: ADCC, anti...

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“…Two other phase I trials also demonstrated robust anti-anti-idiotypic antibody responses to abagovomab but were unable to demonstrate similar clinical responses due to differences in study design. 53,55 Given its overexpression in 90% of ovarian cancers, MUC1 is another promising target for monoclonal antibody therapy. 56 In a phase I trial of 26 women with persistent or recurrent ovarian cancer following platinum therapy, HMFG1, a murine anti-MUC1 antibody, resulted in a small but statistically significant rise in anti-HMFG1 and anti-MUC1 antibody responses in 38% of those completing the vaccination regimen.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…51 Abagovomab (ACA125) is an anti-idiotypic antibody targeting CA125 which has also been examined in ovarian cancer patients. 53,54 Anti-idiotypic antibodies target primary anti-CA125 antibodies and boost the host immune response by mimicking the antigen of interest, producing anti-anti-idiotypic antibodies which also recognize this antigen. 15 In a phase Ib/II trial, abagovomab generated anti-anti-idiotypic antibodies and anti-CA125 antibodies in 68% and 50%, respectively, of 119 patients with advanced ovarian cancer.…”

Section: Cancer Immunotherapymentioning

confidence: 99%