The therapeutic use of antibodies for malignancy

The idea of using the specificity of antibodies to target malignant cells was put forward very soon after the discovery of techniques to generate monoclonal reagents. The responses seen with mouse anti-idiotype in patients with B-cell lymphomas indicated the potential of this approach, but it was some years before key technical obstacles were overcome and the more widespread application of these therapies became possible. Whilst they were originally conceived as having an immunotherapeutic effect, it has become clear that recruitment of immune effectors is only one component of successful antibody therapy, and their action upon the cellular target, either blocking or agonistic, is also critical. The development of immunoconjugates to deliver toxins or radiation is a further extension of the approach, and here again the intracellular effect of antibody ligation appears to be crucial. This presentation will address the central theme of antibody treatments for malignancy that are now reaching the clinic, and will use these examples to highlight ways in which antibodies may be acting in vivo

Treatment of advanced-stage Hodgkin lymphoma

There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%–20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody–drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. © 2016 Elsevier Inc

Differential regulation of cell survival by CD40

The CD40 cell surface receptor is required for normal function of the immune system and is a positive regulator of cell survival for normal B-lymphocytes. However, there is evidence to support both pro- and anti-apoptotic functions for CD40 in malignant B-cells and epithelial cancers. There is increasing interest in the potential of CD40 activating agents as novel therapies for cancer and it is essential to understand the differential response of malignant cells, to inform the design of trials. Here we review the current understanding of differential responses to CD40 activation and apoptosis controlling proteins regulated by CD40 that might account for these effects