The Case for Immunotherapy

Although proposed as a potential therapy for cancer over a century ago, immunological-based strategies have only become a reality in the past two decades. Both the innate and adaptive immune responses are believed to play key roles in tumor surveillance (Diefenbach and Raulet 2002). While innate immunity relies on phagocytes, natural killer (NK) cells, natural antibodies, and complement proteins, adaptive immunity recruits antigen-presenting cells (APC), T cells and B cells (Janeway et al. 2001). As a primeval system of defense, innate immunity depends on invariant receptors recognizing common features of tumor cells, although it has no immunological memory and can often be evaded. The ability to recognize tumors specifically and to prevent their regrowth becomes more efficient with the emergence of adaptive immunity. This property of specificity is based on clonal selection of lymphocytes bearing antigen receptors. A broad range of effector cells, cytokines, chemokines, antibodies, and their recombinant products have been tested in passive immunotherapy in pre-clinical and clinical settings. In addition, tumors and tumor-derived products can be rendered highly effective in stimulating an active immune response.

Like most metastatic solid tumors, stage-4 neuro-blastomas (NB) diagnosed after 18 month of age are often incurable with standard multi-modality therapy. Many of these patients achieve near-complete remissions, only to succumb to tumor recurrence within 4 years from diagnosis. Most pre-clinical models testing various forms of immunotherapy document the greatest efficacy when immunotherapy is applied at the time of small tumor load; thus, application of immunotherapeutic interventions for patients with high-risk NB is likely to be most effective if utilized at the time of minimal residual disease.

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