Immune-based therapies for childhood cancer

• Published in: Nature reviews. Clinical oncology Vol. 11; no. 12; pp. 693 - 703
• Main Authors: Mackall, Crystal L., Merchant, Melinda S., Fry, Terry J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; Nature Publishing Group
• Subjects: 692/699/67/1059/2325; 692/699/67/2332; 692/700/565/251; Cancer in children; Care and treatment; Child; Humans; Immunotherapy; Immunotherapy - methods; Immunotherapy, Adoptive; Medicine & Public Health; Methods; Neoplasms - drug therapy; Oncology; review-article
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2014.177

Key Points Graft-versus-leukaemic effects improve survival following allogeneic stem cell transplantation for childhood leukaemia, and provide proof-of-principle that immune mediated effects can eradicate chemoresistant cancer cells Anti-GD2 monoclonal antibodies can be curative when administered in the setting of minimal residual disease for neuroblastoma, and efficacy requires optimal induction of antibody-dependent cell-mediated cytotoxicity (ADCC) In general, tumour vaccines do not regress established tumours, but can diminish tumour growth or recurrence; randomized studies will be needed to define their efficacy in paediatric cancer Adoptive T-cell immunotherapies have demonstrated efficacy against Epstein–Barr virus-associated lymphoproliferative neoplasms and impressive results have been reported using genetically engineered T cells to treat paediatric leukemia Expansion of the immunotherapeutic armamentarium for paediatric cancers hinges on identification of new immune targets Toxicity associated with immunotherapies is distinct from toxicity associated with cytotoxic agents and small-molecule kinase inhibitors; most common toxic effects include cytokine-release syndrome and autoimmune reactions Immunotherapies for cancer are demonstrating increasing success, and efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Mackall and coauthors discuss the emerging science driving this rapidly moving field and highlight the most pressing challenges that must be overcome for continued progress in this arena, including how to optimize management of novel toxicities associated with these agents and how best to incorporate these therapies into standard treatment paradigms. After decades of research, immunotherapies for cancer are demonstrating increasing success. These agents can amplify existent antitumour immunity or induce durable antitumour immune responses in a wide array of cancers. The spectrum of immunotherapeutics is broad, spanning monoclonal antibodies and their derivatives, tumour vaccines, and adoptive therapies using T cells and natural killer cells. Only a small number of immunotherapies have been tested in paediatric cancers, but impressive antitumour effects have already been observed. Mononclonal antibodies targeting GD2 that induce antibody-dependent cell-mediated cytotoxicity improve survival in high-risk neuroblastoma. Bi-specific monoclonal antibodies that simultaneously target CD19 and activate T cells can induce remission in acute B-cell lymphoblastic leukaemia (B-ALL) and adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors targeting CD19 induce impressive responses in B-ALL. Efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Major challenges include a need to identify immunotherapy targets on the most lethal childhood cancers, to expand availability of technology-intense platforms, such as adoptive cell therapy, to optimize management of novel toxicities associated with this new class of cancer therapies and to determine how best to incorporate these therapies into standard treatment paradigms.