Induction of autoantibodies to cathepsin L as a step towards an anti-cancer vaccine.

Abstract

Cancer is a disease that is caused by mutations in somatic cells. Metastasis is the major cause of death from cancer and often complicates treatment. Malignant tumours secrete degradative enzymes such as cathepsin L which degrade the extracellular matrix to facilitate tumour invasion and metastasis. The immune system does not normally recognize and eradicate tumours because they arise from self tissues to which the immune system is tolerant. Self antigens are poorly immunogenic because they lack T cell help. In this study, a foreign glucosidase was conjugated to self rabbit cathepsin L using glutaraldehyde to specifically provide T helper cell epitopes. The conjugate was used to immunise two male rabbits. A second pair of rabbits (male and female), was primed with sheep cathepsin L (to induce T helper cell activation) and received rabbit cathepsin L boosters. A third pair of rabbits which served as a control was immunised with sheep cathepsin L. The two pairs of test rabbits made high avidity antibodies against rabbit cathepsin L, showing a similar response to control rabbits when antibodies were tested in an ELISA. Western blot analysis showed that these anti-cathepsin L autoantibodies were specific for rabbit cathepsin L. Rabbits which were immunised with the conjugate were · inoculated with sheep cathepsin L nine weeks after the final inoculation with the conjugate. Analysis of antibodies in an ELISA showed that antibody responses against rabbit cathepsin L were augmented in a manner that is characteristic of memory responses. Low titre antibodies against sheep cathepsin L were also produced.