Induction of autoantibodies to cathepsin L as a step towards an anti-cancer vaccine.
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Date
2005
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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 ยท 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.
Description
Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2005.
Keywords
Autoantibodies., Cathepsin., Cancer--Immunotherapy., Glucosidases., Rabbits., Tumours., Theses--Biochemistry.