Recent developments in immunotherapy of acute myeloid leukemia

The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years. Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1) antibody-drug conjugates, (2) T cell-recruiting antibody constructs, (3) chimeric antigen receptor (CAR) T cells, (4) checkpoint inhibitors, and (5) dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results. While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts

Omics analyses provide insights to CART cell therapy resistance

Chimeric antigen receptor T (CART) cell therapy has revolutionized the treatment of relapsed/refractory B cell malignancies in recent years. Despite high initial response rates, durable response rates are low, and CART cell efficacy in solid tumors is very modest. Additionally, the overall success of CART cell therapy is limited by toxicities such as cytokine release syndrome and neurotoxicity. Decades of advancement in genome sequencing technology and bioinformatics have given us a better understanding of how cancer develops and evolves following treatments. This has resulted in a better understanding of patient response to cancer treatment on a molecular level. Resistance to CART cell therapy can be mediated by the cancer cells, the tumor microenvironment, or the patient’s T cells. In this review, we will outline lessons learned from multi-omics studies (1) to identify biomarkers of response or toxicity to CART cell therapy or (2) to develop biomarker-guided therapeutic interventions to overcome these limitations

Laser-air hybrid ultrasonic technique for dynamic railroad inspection applications

The Laser-Air Hybrid Ultrasonic Technique (LAHUT) combines laser generation with air-coupled detection of ultrasound. The technique is non-contact and has the characteristic of operating from remote distances. Acoustic wave laser-generation apparatus can be metres away from the interrogated surface, while air-coupled detection stand-off can be on the order of several centimetres. The technique has the unique capability of interrogating structural materials in their true industrial environment. Dynamic tests are performed on parts with complex geometry, limited accessibility and curved surfaces. Also, dark and rough finish surfaces, which significantly reduce the efficiency of optical detection techniques, can be interrogated successfully. These characteristics make the LAHUT ideal for many industrial applications including the rail industry. It was developed for railroad inspections targeting the most critical cracks in rails and wheels. State-of-the-art inspection techniques available to the rail industry often miss Vertical Split Head (VSH) and Transverse Detail Defect (TDD), which lie in unfavourable positions and orientations in the rail head. No method exists to perform dynamic inspections of the rail base or any part of the railroad wheel. Laboratory experiments were performed for the detection of TDD and Proof Of Concept (POC) field tests were performed for VSH, rail base cracks, thermal fatigue cracks along the wheel flange and tread and subsurface Shattered Rim Cracks (SRC) along the wheel tread. The results were successful and highly repeatable. The technique lennds itself for digital collection anal automated processing of data, making the LAHUT a very strong candidate for next-generation rail inspection technique