Adoptive immunotherapy: a new era for the treatment of cancer.

Abstract

The early promise of adoptive immuno­ therapy is now coming to fruition with excit­ ing clinical responses being reported against various cancers. This has particularly been the case with adoptive transfer of tumor­infiltrat­ ing lymphocytes in patients with advanced malignant melanoma [1–3], transfer of chime­ ric antigen receptor (CAR) T cells targeting CD19 in patients with B­cell malignancies such as chronic lymphoid leukemia and acute lymphoblastic leukemia [4–7] and transfer of Epstein–Barr virus (EBV)­specific T cells against viral­induced malignancies such as post­transplant lymphoproliferative disorder (PTLD) [8,9]. However, for application of adoptive cellular therapy to a wider range of solid and hematological cancers, several chal­ lenges remain. In this special focus issue, we have invited several experts in the adoptive immunotherapy field to discuss these issues and propose potential strategies for enhancing the current success of this approach. Smith and Khanna discuss the use of adop­ tive T­cell therapy for EBV­induced cancers. This therapy has been very successful for PTLD, however, this is currently not the case for other EBV­induced cancers includ­ ing lymphoma and nasopharyngeal cancer. This review discusses various new strategies for altering the tumor microenvironment and increasing tumor immunogenicity. This includes adjunct­based approaches involving chemotherapy in combination with adop­ tive T­cell therapy which has shown some promising signs against nasopharyngeal can­ cer. Alternatively, targeted approaches for preferentially expanding T cells recognizing EBV­associated antigens LMP­1, LMP­2 or EBNA1 have showed some promising results in lymphoma patients. Beavis et al. discuss the negative effect of immune suppression pathways on the effi­ cacy of adoptive T­cell therapy. The recent success of immune checkpoint inhibitors blocking PD­1 and CTLA­4 pathways in patients with advanced cancer such as melanoma, renal cancer and non­small­ cell lung carcinoma suggests that immuno­ suppression can be effectively overcome resulting in increased antitumor immunity in some patients. This has raised the pos­ sibility that combining these drugs with other immunotherapies including adoptive T­cell immunotherapy may lead to further enhancing antitumor effects in patients par­ ticularly for less immunogenic cancers. This review discusses several nongenetic and genetic strategies that may be employed to overcome tumor­induced immune suppres­ sion for enhancing the efficacy of adoptive Adoptive immunotherapy: a new era for the treatment of cancer