Oxford BioMedica PLC (OXBDF)

[marcusl2]

They are starting to say curative now re blood cancers ! Exciting days ahead. The Novartis guy I believe was mentioning OXB re Lentivirus production. His view on pricing was interesting. He also predicts some success with solid tumours.

5T4
The oncofetal antigen 5T4 was identified by screening for shared surface molecules in human trophoblasts and human cancer cells [Stern et al. 2014]. A heavily glycosylated, membrane-bound protein, 5T4 is highly expressed in cervical, colorectal, gastric, ovarian, prostate, lung and renal cancers [Southall et al. 1990]. The expression of 5T4 has been associated with epithelial mesenchymal transition (EMT), which is involved in the metastasis of epithelial cancers [Nieto and Cano, 2012]. Three different 5T4-based immunotherapeutic strategies are being clinically evaluated: a vaccine known as TroVax® (modified vaccinia virus Ankara- MVA), an antibody–superantigen [Staphylococcal Enterotoxin A (SEA)] fusion protein, and an antibody–drug conjugate (ADC) combining a 5T4-specific monoclonal antibody with a tubulin inhibitor.

5T4 vaccine (TroVax®)
Favorable trends toward clinical benefit have been observed in early phase I and phase II clinical trials of the TroVax® 5T4-MVA vaccine in advanced RCC [Zhang et al. 2012], CRC [Rowe and Cen, 2014], and castration-resistant prostate cancer [Harrop et al. 2013]. To determine whether treatment with TroVax® can improve survival, a phase III clinical trial in patients with metastatic RCC compared treatment with TroVax® to standard of care treatment [Amato et al. 2010]. While this trial failed to demonstrate any significant effects of TroVax® on OS, a subgroup of patients with good prognosis and receiving concurrent IL-2 experienced a significant survival benefit compared with placebo. The patients with the greatest increases in 5T4-specific antibodies also experienced a survival benefit with TroVax® compared with placebo, which is consistent with a pooled analysis of prior phase I/II TroVax® studies [Harrop et al. 2010].

5T4 superantigen–antibody fusion protein (naptumomab estafenatox)
The tumor-targeted super-antigen concept employs bacterial superantigens, which are the most potent known activators of T cells, to attract and activate large numbers of T cells to the target [Eisen et al. 2014]. A phase II study of the superantigen-antibody fusion protein targeting 5T4 in RCC showed a significant survival benefit [Shaw et al. 2007], which led to the development of ANYARA (naptumomab estafenatox) [Eisen et al. 2014]. Naptumomab estafenatox has been evaluated in combination with interferon a in a phase II/III clinical trial involving patients with advanced RCC. Although the study failed to meet its primary endpoint, survival benefits were seen in a subgroup of patients with low levels of IL-6 and normal levels of SEA antibodies [Elkord et al. 2015]. The results of this study are still undergoing analysis, and a phase II/III clinical trial of naptumomab estafenatox in combination with a TKI for metastatic RCC is being designed [Stern et al. 2014]. Lastly, promising preclinical activity has been seen with an ADC targeting 5T4 [Sapra et al. 2013], and clinical evaluation is now underway [Stern et al. 2014].