Title:
|
Idiotypic vaccination against a B-cell lymphoma
|
The idiotypic determinants carried on the surface of most B cell tumours are capable of acting as highly specific tumour associated antigens. In two previous models of lymphoma, active immunisation with purified idiotypic immunoglobulin has generated a specific anti-idiotypic response which suppressed tumour development. This phenomenon has been further explored using a different model of B-cell lymphoma, the A31 lymphoma, which involves cells with properties closer to those of the human counterpart. Pre-immunisation of CBA/H mice with idiotypic IgM derived from the A31 lymphoma was shown to specifically protect these animals from a subsequent tumour inoculum. The protection generated was strong: no immunised animal showed any sign of lymphoma development during more than 100 days after tumour challenge, even when challenged with a high tumour dose (5x10⁵ A31 cells). The control groups immunised with unrelated IgM showed no such protection and all these animals succumbed to a lymphoma challenge after about 20 days. Anti-idiotypic immunity persisted for several months, since a second exposure to a lethal tumour dose 4 months after the first challenge failed to induce lymphoma. Anti-idiotypic antibody appeared to have a major role in protection. Evidence for this came from passive transfer experiments. In contrast, no contribution from immune cells could be identified via passive transfer experiments. Protected mice were investigated for the presence of lymphoma cells 408 months after exposure to tumour but the spleens, which were of normal weight and appearance, contained few or no tumour cells by phenotypic analysis. The few cells that were detected were present in an anatomically normal location within the spleen and were considered to be held under some form of growth restraint. This dormant state was only broken on passage of these cells into unimmunised recipients. In 60% of cases splenocytes from long-term survivors caused tumour development in the naive recipients. In these cases the emergent tumours were indistinguishable from the original A31 lymphoma with no evidence for any variants.
|