Abstract
Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence.
Highlights
An in vitro experiment using murine acute myeloid leukemia (AML) cells demonstrated that co-expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and Programmed Cell Death 1 (PD-1) on CD8-positive T cells was enhanced during disease progression and inhibition of either molecule alone did not attenuate tumor activity [35]
Clinical experience of immune checkpoint inhibitors (ICIs) in solid tumors has shown that IO therapy brings long-term disease control in at least
Concomitant use of chemotherapy and/or radiation could enhance the efficacy of IO therapy [136,137], it has not yet been proven in hematologic malignancies
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The first-in-class CD19-targeted CAR-T tisagenlecleucel ( known as tisa-cel) was approved by the FDA for relapsed/refractory B-ALL in August. A multicenter phase 1/2 study ZUMA-1 showed somwhat better response rates (82%) of another CD19-targeted CAR-T axicabtagene ciloleucel ( known as axi-cel) for refractory DLBCL [7]. For CD33-positive AML, GO showed an overall response rate of 63% in relapsed/refractory cases [8], along with survival benefit in newly diagnosed cases when combined with conventional chemotherapy [9]. As immune inhibitory molecules and cancer-related antigens on leukemic cells have been discovered, novel IO drugs have been recently developed in the field of AML and are expected to become another treatment option. Recent representative advantages in terms of IO therapy are summarized in this review
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
