CR and CRi were observed in 34 (78%) of 44 patients, including 18 cases in which their minimum residual disease (MRD) was undetectable after completion of the induction therapy. retargeting (DART), trispecific killer cell engager (TriKE), chimeric antigen receptor (CAR) Thiotepa == 1. Introduction == Since the Food and Drug Administration (FDA) approved ipilimumab, the first-in-class anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) antibody, for melanoma in March 2011 [1], immune checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, atezolizumab, and durvalumab have been eagerly developed and are now practically available for a variety of malignant tumors. For the majority of solid tumors, immuno-oncology (IO) therapy has been involved in mainstream cancer treatment along with molecular targeted therapy, conventional chemotherapy, and radiation therapy. In the field of hematologic malignancies, the first bispecific T-cell engager (BiTE) blinatumomab, a CD19- and CD3-targeted bispecific antibody, achieved complete remission with 6.7 month-long duration in 32% of the patients with B-cell lymphoblastic leukemia (B-ALL) in a clinical study [2] and has shown efficacy in non-Hodgkin lymphomas (NHLs) [3,4]. Currently, chimeric antigen receptor (CAR)-T therapy also accounts for an essential a part of IO therapy against hematologic malignancies. The first-in-class CD19-targeted CAR-T tisagenlecleucel (also known as tisa-cel) was approved by the FDA for relapsed/refractory B-ALL in August 2017 and diffuse large B cell lymphoma (DLBCL) in May 2018, with overall remission rates of 83% and 52%, respectively [5,6]. A multicenter phase 1/2 study ZUMA-1 also showed somwhat better response rates (82%) of another CD19-targeted CAR-T axicabtagene ciloleucel (also known as axi-cel) for refractory DLBCL [7]. Traditional monoclonal antibodies (e.g., rituximab, alemtuzumab, obinutuzumab, and mogamulizumab) and antibody-drug conjugates (ADCs) (e.g., gemtuzumab ozogamicin (GO) and brentuximab vedotin) are also used in IO therapy. Novel brokers of CAR-Ts, ADCs, and bispecific antibodies are currently under development. Intensive chemotherapy (e.g., anthracyclines and cytarabine) with or without hematopoietic stem cell transplantation (SCT) has been the mainstay of the curative treatment of acute myeloid leukemia (AML), presenting a dismal prognosis for relapsed/refractory or intolerable cases which mostly require palliative care. For CD33-positive AML, GO showed an overall response rate of 63% in relapsed/refractory Thiotepa cases [8], along with survival benefit in newly diagnosed cases when combined with conventional chemotherapy [9]. Due to the paucity of favorable immune targets in leukemic cells, IO approaches for AML have been limited. However, 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. == 2. Molecules Involved in IO Therapy == == 2.1. Immune Checkpoint Molecules == == Rabbit Polyclonal to PEX14 2.1.1. Programmed Cell Death 1 (PD-1), Programmed Cell Death-Ligand Thiotepa 1 Thiotepa (PD-L1), and Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) == The inhibitory surface receptor programmed cell death 1 (PD-1) (UniProtKB-Q15116) on activated T cells is usually encoded by thePDCD1gene on chromosome 2q37.3. Along with its ligands PD-L1 and PD-L2, also known as CD274 and CD273, PD-1 plays an important role in maintaining self-tolerance [10] and is often involved in immune escape in cancer by inhibiting the direct cytotoxic activity of effector CD8-positive T cells on tumor cells [11]. CTLA-4 on activated T cells, which is usually encoded by the CTLA4 gene on chromosome 2q33.2, also has a.