Immune Adjuvants

Immune adjuvants can be classed as:

• Non-specific, e.g. BCG vaccine for bladder cancer.

• Specific, e.g. Salk vaccine for polio prevention.

• Genetic, to elicit cytokine responses (vide infra).

Vaccines, used widely in medicine since Jenner's pioneering work in preventing small pox by inoculating intradermal cow pox virus, are probably the best examples of the broad application of biotechnology products prior to the twentieth century. Traditionally, vaccines have been directed against the prevention of specific infectious diseases. Attenuated live and killed microrganisms are used as antigens to elicit cellular and humoral responses. They may be viewed as adjuvants, because it is the enhanced endogenous physiology that protects against the pathogen, and not the material in the vaccine itself.

The potential for preventing infectious disease is far from complete, and there is a continuing need for worthwhile research programs. Current challenges include HIV and prion-mediated disease, although the latter may (controversially) also be regarded as 'autoimmune' or 'congenital' when it is due to the derepression of prion genomes, which lurk dormant in many normal mammals. The numerous diseases that plague tropical countries and the developing world provide much scope but little financial incentive to the traditional pharmaceutical industry. Drug resistance, occurring in numerous microorganisms ranging from staphylococcus to malaria, is another field that could conceivably be conquered by taking the adjuvant approach.

Not surprisingly, there is considerable interest in using adjuvant tactics for the prevention or treatment of non-infectious disease. Spontaneous tumor regression (although rarely observed clinically) and the development of rare tumors in immunocom-promised patients (such as Kaposi's sarcoma in patients with AIDS) are both consistent with the usefulness of endogenous host mechanisms to either prevent or retard cancer. Tumor-specific antigens may be used as therapeutic targets for exogenous therapy.

There is a broad range of mechanisms against these targets, such as specific cytokines, tumor cell expression of rejection antigens and inducing lymphocyte co-stimulatory molecules on tumor cells (vide infra). Non-specific approaches also exist, e.g. Bacille Calmet-Guerrin vaccine (BCG), which elicits a T lymphocyte cell-mediated immune response, can be used not only to prevent tuberculosis but also to (non-specifically) prevent the recurrence of bladder cancer.

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