Monoclonal antibodies and vaccines are establishing themselves as a possible mainstay of cancer therapy. There are many licensed products targeting a range of cancers. Most of these mabs either block growth factors or cause direct killing. It is known that many mabs also induce ADCC and CDC. However, the role of immune effector functions in anti-tumour responses remains unsure. In the tumour microenvironment, there are profound immunosuppressive cells and mechanisms such as tumour promoting macrophages expressing inhibitory Fc receptors or lack of NK cells that could mediate ADCC. This environment is also a problem for cancer vaccines. Although they may stimulate strong T cell responses, effector and memory T cells are attenuated or killed in the tumour environment. The new class of immunomodulatory mabs have been addressing some of the problems. The anti-CTLA-4 mab, YERVOY, blocks T cell inhibition and results in regression of bulky disease in 10-20% of melanoma patients. Unfortunately this comes at a cost, in part, of strong autoimmunity, which can however be controlled with specific therapy. The new class of anti-PD.1/PD-L1 mabs, which act at the tumour site and are less toxic, represent further progress. Similarly cancer vaccines stimulating potent pro-inflammatory CD4 responses can reverse the immune suppressive tumour environment and support efficient anti-tumour responses. Infections are successfully defeated by combined T cell and antibody responses. Therefore it seems plausible that mabs and vaccines may synergise to provide optimal anti-tumour immunity. This CAVAD 2014 conference brings together experts in both fields of mabs and vaccines to address these important issues.
Abstracts are called for both oral and poster presentation – please refer to the participation section for details.
Scientific Advisory Panel
Lindy Durrant (University of Nottingham, Nottingham, UK)
Daniel Speiser (Ludwig Institute/University of Lausanne, Lausanne, Switzerland)
Martin J. Glennie (University of Southampton, Southampton, UK)
Haval Shirwan (University of Louisville, Lousiville, Kentucky, USA)
Peter L. Stern (University of Manchester, Manchester, UK)
Simon Draper (University of Oxford, Oxford, UK)
Dietmar Zehn (CHUV, Lausanne, Switzerland)
Mark C. Glassy (IMRF, San Diego, California, USA)
Jeffrey A. Hubbell (EPFL, Lausanne, Switzerland)
John Lambert (ImmunoGen Inc., Waltham, Massachusetts, USA)
Alena Donda (University of Lausanne, Lausanne, Switzerland)
Niranjan Sardesai (Inovio Inc., Blue Bell, Pennsylvania, USA)
John Haurum (F-star, Cambridge, UK)
Francois Spertini (CHUV, Lausanne, Switzerland)
Ronald Rooke (ElsaLys Biotech, Illkirch, France)
John-Edward Butler-Ransohoff (Bayer Innovation GmbH, Leverkusen, Germany)
CAVAD 2014 will include keynote presentations from leading researchers, submitted oral and poster presentations, and special discussion/panel sessions. Please refer to the participation section for details.
Abstracts for both oral and poster presentation are called for in the principal topics to be covered at CAVAD 2014 which include:
Autoimmunity and cancer
Both mabs and vaccines are trying to harness the immune system to recognise and attack self/modified antigens on cancer cells. As autoimmunity does this very effectively, inducing both T cell and antibody responses, there are good lessons to learn for cancer immunotherapy.
As vaccines target intracellular antigens, presented as peptides on MHC molecules, and Mabs target cell surface proteins there is obvious synergy in combining these approaches. Indeed both cellular and humoral immunity are used in the successful attack on pathogens.
There are still very few approved adjuvants for vaccines that stimulate cellular immunity, however new TLR agonists are being developed and the recent approval of a mab targeting CTLA-4 and trials with anti-PD.1 mabs suggest novel approaches/combinations.
High avidity CD8 T cells, cytotoxic CD4s and direct killing/growth inhibiting mabs have all been shown to mediate potent anti-tumour responses.
MDSC, Tregs, M2 macrophages, M2 fibroblasts, IL-10 and TGFbeta amongst other factors have been shown to create an immunosuppressive tumour environment switching off T cells and reducing the efficacy of ADCC and CDC mediated by mabs. Neutralising these cells/factors with approaches such as anti-PDL1 mabs are showing great promise.
Recent results have suggested that CD4 cells are not terminally differentiated and can be converted from iTreg to Th1 cells suggesting that vaccines/mabs that promote this switch may have powerful anti-tumour effects.
Cancer stem cells
Cancer stem cells have the capacity to repopulate tumours if not targeted efficiently by immunotherapy. Vaccines and mabs targeting cancer stem cells will be presented.
Chemotherapy and radiotherapy can relieve the immune suppressive tumour microenvironment making vaccines and mabs more effective.
Vaccine/mab delivery vehicles