Good progress has been made towards achieving the milestones set out in the original application. Four clinical trials with reagents, developed in Southampton have completed recruitment: the anti-CD40 antibody study (18 patients), the DNA vaccine studies in lymphoma, prostate cancer (32 patients) and CEA expressing malignancies (30 patients). The final study reports on these latter studies will be published in 2010 and the data show that the vaccines are not only immunogenic but also appear to confer some clinical benefit. The laboratory evaluations of these studies are being or have been undertaken in Southampton and ECMC support for this has been critical.
As a result of these studies a new tranche of trials are in development: a randomized phase II DNA vaccine study in CML is due to open recruitment in the 1st half of 2010. The data from our current DNA vaccine studies in prostate and CEA expressing cancers also have led to a new collaboration with Oxford (Hatton, Banham, Pulford) to develop and clinically test a DNA fusion vaccine against two immunogenic epitopes from a novel tumour target,PASD1, for which the Oxford and Southampton teams have preclinically shown immunogenicity in mouse and human systems. A combination of a vaccine with anti-CD40 is in the protocol development stage.

Southampton will lead a multicentre investigator phase II study will examine the effect (clinical and immunological) of the addition of an immunostimulatory antibody directed against CTLA-4 (Ipilimumab, Bristol Meyer Squibb) to standard chemotherapy. Academically the careful examination of immunological consequences of this concept will be at the heart of the study; recruitment of the 1st patient is expected in the 1st half of 2010.Southampton is the lead centre for a novel anti-CD19 antibody (Merck) is being developed for testing in B-Cell lymphoma. This investigator led, DDO sponsored study is expected to open during 2011.

Our collaborative RIT programmes in haematological malignancies (anti-CD66) and B-cell tumours (anti-CD20 CD22 and CD25 in lymphomas) continue to thrive, with three national phase II studies open. A DDO sponsored study of antiCD25 I131 in relapsed Hodgkin’s disease is currently in set up in partnership with UCLH (lead) and Manchester.

A number of early phase trials with industry (e.g. CMC544, anti CCL2, anti-IL6, anti CD4, ofatumumab, non-fucosylated antiCD20, panobinostat, Depsipeptide and lenalidamide) have completed recruitment or are actively recruiting and these collaborations have significantly expanded our portfolio of early translational studies beyond the scope anticipated in our application. Of note these studies recruit(ed) patients with lymphoma and a broad range of solid tumours, resulting in a desired broadening of cancer types targeted.

We have completed participation in and continue to recruit to a broad portfolio of phase I/II studies of small molecules, such as tyrosine kinase inhibitors, in mainly industry sponsored research and solid tumours and lymphomas

• The anti-CEA DNA vaccination has almost completed follow up with 2 patients due their last visit in 03.10. The interim data analysis suggests that time to disease progression is longer in immune responders and patients who have developed signs of gastrointestinal adverse events.
• The anti-CD40 has completed recruitment at the top level of dose escalation (160mg/dose) and as a result of the excellent safety profile we are developing the next trial, to combine the anti-CD40 antibody with a DNA vaccine.
• The collaborative RIT programme with Manchester, UCL and is recruiting rapidly in phase II studies with an expanding trials in lymphoma and myeloma, targeting CD22, CD19, CD25 and CD66 resulting in the largest European RIT portfolio. New preclinical data (Ivanov et al, J Clin Invest. 2009;119:2143-59) is expected to feed into early clinical testing in the foreseeable future.
• Our multicentre randomized phase II DNA vaccination study in haematological malignancies (CML) has obtained LRF funding and is now adopted onto the NCRI trials portfolio. Expected data for first patient on study is April 2010.
• The study of an anti CD22 directed immunotoxin (CMC-544) has completed with highly encouraging results in patients with follicular lymphoma and diffuse large cell lymphomas, reported at ASH 2009. Southampton was the lead UK centre.A novel anti-CD19 antibody is being worked up for clinical testing in late 2010 under the auspices of the DDO.
• We have reported new data on the biology of CNS lymphomas, which identify circulating tumour in blood and bone marrow and shed new light on the biology of this disease (McCann et al, Blood. 2009;113(19):4677-80).