A Pilot Study of MUC-1/CEA/TRICOM Poxviral-Based Vaccine in Patients with Metastatic Breast and Ovarian Cancer

Abstract

Purpose PANVAC is a recombinant poxviral vaccine that contains transgenes for MUC-1, CEA and 3 T-cell costimulatory molecules. This study was conducted to obtain preliminary evidence of clinical response in metastatic breast and ovarian cancer patients. Experimental design Twenty-six patients were enrolled and given monthly vaccinations. Clinical and immune outcomes were evaluated. Results These patients were heavily pretreated, with 21 of 26 patients having ≥ 3 prior chemotherapy regimens. Side effects were largely limited to mild injection-site reactions. Breast cancer: For the 12 patients enrolled, median time to progression was 2.5 months (1 – 37+) and median overall survival was 13.7 months. Four patients had stable disease. One patient had a complete response by RECIST and remains on study ≥ 37 months, with a significant drop in serum IL-6 and IL-8 by day 71. Another patient with metastatic disease confined to the mediastinum had a 17% reduction in mediastinal mass and was on study for 10 months. Patients with stable or responding disease had fewer prior therapies and lower tumor marker levels than patients with no evidence of response. Ovarian cancer:Median time to progression for patients (n=14) was 2 months (1 – 6) and median overall survival was 15.0 months. Updated data are presented here for one patient treated with this vaccine in a previous trial, with a time to progression of 38 months. Conclusions Some patients who had limited tumor burden with minimal prior chemotherapy appeared to benefit from the vaccine. Further studies to confirm these results are warranted.

Harnessing the immune system for the treatment of breast cancer

“…Together, these data suggest that breast cancer vaccines may have the highest efficacy when combined with other therapeutic modalities. Consistent with earlier findings showing an inverse correlation between prior chemotherapy and the efficacy of vaccine treatment (von Mehren et al, 2000;, a recently reported pilot study of a MUC-1/CEA/TRICOM poxviral-based vaccine showed that only 1 of 12 patients with breast cancer had an objective complete response, whereas all the others had rapid progression of disease (Mohebtash et al, 2011). The only responder was a patient who had minimal disease and was not as heavily pretreated as the others, suggesting that breast cancer vaccine monotherapy in patients with heavy tumor burdens or extensive prior treatment with chemotherapy is not likely to produce a significant clinical benefit.…”

Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer

“…In breast cancer, a phase II study is conducted in the neoadjuvant setting by the Austrian Breast and Colorectal Cancer Study Group (ABCSG-34 trial). Two other tumor vaccines targeting MUC1 have been developed that are currently tested in clinical trials [27,28]. Antibodies targeting MUC1 have had limited success so far, maybe due to the presence of circulating MUC1 in patient serum.…”

Immunooncology in Breast Cancer: Active and Passive Vaccination Strategies

“…PANVAC TM (Therion Biologics Corp., Cambridge, MA, USA) targets both MUC-1 and CEA; it uses viral vectors to deliver the antigen together with 3 human T-cell costimulatory molecules [16]. In early clinical trials in heavily pretreated patients, the vaccine demonstrated some clinical activity, including a complete response [17,18].…”