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European Biopharmaceutical Review

Improving Tumour Immunity

Dr Kostas Kosmatopoulos of Vaxon-Biotech and Dr Jean-Pierre Abastado at the Laboratory for Tumour Immunology, Singapore Immunology Network, approach the promising future of antitumoural immunity

Prophylactic vaccines against infectious diseases are one of the most brilliant achievements of modern medicine and immunology. Harnessing the immune system in a similar way to fight cancer has been the holy grail of tumour immunologists since Coley’s initial attempts in the late 19th century. Unfortunately, the course of cancer immunotherapy research has, until now, been marked by more disappointments than successes.

However, several significant achievements have rekindled optimism in recent years. Encouraging clinical results have been obtained not only with immunostimulants such as anti-CTLA-4 monoclonal antibody (mAb) (1) and ODN-CpG (CpG7909) (2) that non-specifically stimulate strong immune responses, but also with active- and adoptive-specific immunotherapy.

Firstly, certain vaccines (BLP-25, Provenge) (3,4) have been shown to enhance overall patient survival in randomised Phase IIb/III clinical studies. Secondly, potent immune responses were shown to correlate with a survival benefit in vaccinated patients participating in recent clinical trials (5,6).

Thirdly, spectacular and long-lasting clinical responses (complete and partial regression of primary tumours and metastases) have been obtained in metastatic, previously lymphodepleted melanoma patients adoptively transferred with large numbers of high-affinity antimelanoma cytotoxic T lymphocytes (CTL) amplified in the laboratory (7). All of these observations show that triggering a potent and high-affinity antitumoural immune response is a precondition for clinical efficacy. This is now the key challenge in tumour vaccine research.

CYTOTOXIC T LYMPHOCYTES (CTLs)

CTLs are currently considered to be the main effectors of antitumoural immunity, and tumour vaccination therefore aims to generate large numbers of high-affinity CTLs. CTL stimulation requires two distinct signals. Signal one is delivered through the T cell receptor (TCR) after its engagement with an antigen presented in association with class I human leukocyte antigens (HLA-I) expressed by dendritic cells (DCs).

Signal two is delivered through receptors, such as CD28, that are expressed by CTLs after their interaction with costimulatory molecules expressed by DCs (B7 family) (see Figure 1). DCs must first be activated to express these costimulatory molecules, and this can be achieved by the engagement of CD40 molecules or toll-like receptors (TLR), for example.


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Kostas Kosmatopoulos, MD, PhD, is Chief Scientific Officer of Vaxon-Biotech. Kostas was Research Director at the Institut National de la Santé et de la Recherche Médicale (INSERM) and head of a laboratory which specialises in tumour immunotherapy at the Gustave Roussy Institute, Villejuif, France. He has co-authored more than 40 peer reviewed scientific publications and filed seven patents.

Jean-Pierre Abastado, PhD, heads the Laboratory for Tumour Immunology at the Singapore Immunology Network. He has worked at the Pasteur Institute, the Cochin Institute (Paris) and at NIH (Bethesda, US) and is Research Director at the Centre National de la Recherche Scientifique. From 1998 to 2005, Jean-Pierre was Vice President and Chief Scientific Officer of IDM-Pharma and is the author of more than 100 scientific publications and 10 patent applications.

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Kostas Kosmatopoulos
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Jean-Pierre Abastado
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