Melanoma is considered one of the immunogenic - if not the most immunogenic -
malignancies. This is based on several observations.1.Spontaneous remissions occur occasionally.2.In about 5% of
melanomas no primary tumour is found. The genetic aberrations of these tumours closely resemble those of cutaneous
melanomas, and therefore are suggestive of
spontaneous regressions of the primary tumours.3.Both primary tumours and
metastases often have brisk lymphocytic infiltrates, a phenomenon that is correlated with better outcome.4.Studies of isolates of these tumour-infiltrating T lymphocytes have revealed that a proportion of these cells recognise
melanoma antigens.5.
Melanomas respond to
immunotherapy. These observations have led to over 30 years of research on
immunotherapy for
melanoma; many of these efforts have failed, with only a few exceptions:
interleukin-2 (IL-2) and to a lesser degree
interferon-a (IFN-〈). Recently, new developments in
immunotherapy have revolutionised this treatment modality. Anti-CTLA4 has received approval from the Food and Drugs Administration (FDA) and the European Medicines Agency (EMA) for the treatment of stage IV
melanomas based on the improvement in overall survival in phase III trials, and more recently blockade of PD1/PDL1 interactions has shown objective clinical responses in a stage IV
melanoma in early-phase clinical trials. In addition, several independent single-institution phase I/II trials using adoptive
cell therapy have shown a consistently high response rate, including durable complete remissions in a substantial percentage of treated patients. Now, for the first time,
immunotherapy has moved beyond the treatment of
melanoma as both CTLA4 and PD1 blockade have been shown to induce objective responses in other tumour types as well. This chapter will discuss the mechanism of action, clinical efficacy and side effects of
IL-2, the novel treatments consisting of the
immune checkpoint blockade drugs anti-CTLA4 and anti-PD1 and adoptive
cell therapy.