Distinct immune therapies for high-risk NBL and MEL are in clinical testing. Some are technologically complex and difficult to deliver to the many patients potentially needing them each year, while others have limited applicability. Large phase III trials are needed to determine which can improve disease free and overall survival in MEL and NBL patients, particularly those put into remission with standard therapy, but with a high likelihood of relapse. Hu14.18-IL2 offers the advantages of long-term storage, ease of ordering and administration, broad patient applicability (without limitations due to HLA-phenotype of patient, as for certain vaccines), and the ability to induce both NK and T-cell mediated antitumor effects. With toxicity studies completed demonstrating acceptable profiles, and phase II studies showing some antitumor activity, subsequent studies are being planned to evaluate anti-tumor activity in patients with minimal disease, the setting where IC has been noted in preclinical animal studies to be the most useful. Also, preclinical studies are investigating mechanisms of IC in terms of antitumor effect where intratumoral administration of IC has better therapeutic effect on both primary and distant tumors. Further studies will need to address optimal administration, given the difficulty with multiple intratumoral injections if translated to the clinical setting for patients with tumors that are not readily accessable for injection. Also, regimens adding IC therapy to various chemotherapeutics or other immune therapies are being explored in preclinical settings. Given the dramatic antitumor effects seen in preclinical studies and the initial results seen in phase I and II clinical trials, continued clinical testing and development of hu14.18-IL2 should continue.