Generation of tumour-rejecting anti-carbohydrate monoclonal antibodies using melanoma modified with Fas ligand.

Carbohydrate antigens such as glycolipids and glycoproteins are over-expressed in a variety of cancers and have therefore been identified as ideal candidates for tumour vaccines. Detection of anti-carbohydrate antibodies is associated with a good prognosis in cancer patients. However, generation of an efficient adaptive immune response has been hampered by the low immunogenicity of carbohydrates due to tolerance. Here, we describe a method by which tumour-rejecting antibodies directed against carbohydrates can be elicited in two different melanoma mouse models. Thus, using the murine melanoma B16F10 over-expressing Fas ligand (FasL), we have generated mAbs against cancer carbohydrate antigens expressed by the melanoma. Importantly, passive transfer of mAbs resulted in rejection of melanoma in vivo. Their protective effect in vivo was dependent on FcR and in vitro antibody-dependent cellular phagocytosis. They were also able to delay tumour growth when injected after the tumour was established. FasL-expressing tumours as an adjuvant are a novel way to generate anti-carbohydrate antibodies able to reject tumours in vivo.

Characterisation of monoclonal antibodies to the TNF and TNF receptor families.

Tumour necrosis factor (TNF) family ligands and their corresponding receptors play important roles in the immune system and are involved in immune regulation such as lymphoid development, cell proliferation, differentiation, activation and death. Antibodies against these ligands and receptors together with Fc-fusion proteins, have been particularly useful as immunological tools in addressing the underlying involvement of these proteins in these contexts and furthermore, have given us hope in using them as potential therapeutic agents. Over last few years, there have been many additions to these ever-growing TNF family ligands and their receptors. Here, we have generated and characterised a set of monoclonal antibodies, together with mAbs from the HLDA workshop, against DcR1, DcR2, DR4, DR5, TRAIL, APRIL, BAFF, BAFF-R, BCMA, and TACI, which may be useful in phenotypic and functional studies of the role of TNF and TNF receptor family in immune function and regulation in relation to health and disease.