Eskandari M, et al. Blood Res. 2019 Jun;54(2):114-119. https://doi.org/10.5045/br.2019.54.2.114

Introduction: A new type of immune cell transplantation called allogeneic NK cell infusion is proposed as a potential universal off-the-shelf cell product for adoptive immune cell therapy in hematologic malignancies. Design: A multicentral phase I non-randomized clinical trial was conducted to assess the safety, feasibility, and potential efficacy of adoptively infused NK cells in patients with refractory/relapsed AML. We evaluated the feasibility of the trial by considering cell production, patient selection, and treatment protocol. Method: Allogeneic NK cells were produced from random healthy unrelated donors; 10 patients were selected according to the inclusion criteria and were included in two groups in case of NK cell dose escalation. Two cell infusions were given, spaced 7 days apart, following a lymphodepletion conditioning regimen of fludarabin-endoxan administered 7 days before the first infusion. The intervention safety was scored using Common Terminology Criteria for Adverse Events (CTCAE) based on variations in vital signs due to cell infusion. NK cell chimerism, tumor burden, and duration of relapse were considered to be components of efficacy. The pilot feasibility evaluation was checked using the CONSORT platform. Results: The NK cell infusion procedure was well tolerated, and no grade 2–5 toxicities related (possible or probable) to PB-NK cell infusion were observed. Four patients developed grade 1 transient chills, headaches, vomiting, and bone pain following each PB-NK cell infusion that were not required hospitalization. One of these patients (p01) died because of severe acute respiratory syndrome. Of 9 evaluable patients, 6 (66.6%) showed stable disease (SD) and 3 (33.3%) presented progressive disease (PD). Of 6 SD patients, 2 (p08 and p09) remained alive in SD and 3 patients (p04, p05 and p07) converted to PD at 9 months after infusion of NK cells, and 1 (p03) was not evaluable due to follow-up loss. No patient achieved complete remission. Conclusion: The study demonstrated the feasibility and safety of adoptive transfer of random healthy unrelated donor PB-NK cells in refractory/relapsed AML patients and supports continued study in phase II clinical trials in relapsed/refractory AML patients.

Allogenic chimeric antigen receptor T (CAR-T) cells have advantages compared to autologous T cell therapies such as availability cells for production, a suitable HLA-matched donor (if graft-vs-host-disease and rejection effects are to be avoided and also lower risks associated with transduction methods in process of autologous CAR-T cells). In recent years, the additional editing and non-editing technologies are helping to make allogenic CAR-T therapies a hopeful future treatment. Universal off-the-shelf CAR-T cells can be solved key issues include preventing graft-versus-host disease (GVHD) and time consumption and other challenges faced to allogenic CAR-T cells. Here, we have highlighted the improvement in CAR-T development, particularly in engineering allogenic CAR-T, clinical practices related to these, pre-clinical and clinical studies and their successes which investigated in recent 10 years related to treatment of hematological malignancies and cancers by allogenic CAR-T cells.

The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML.

Hematological malignancies present significant therapeutic challenges, often complicated by drug resistance, poor bioavailability, and systemic toxicity of conventional treatments. Engineered exosomes have emerged as promising therapeutic carriers, offering unique advantages over synthetic nanoparticles through their natural biocompatibility, enhanced barrier penetration, and intrinsic cell-targeting capabilities. This review examines recent advances in exosome engineering strategies for hematological malignancy treatment, encompassing both parental cell-based modifications and direct engineering approaches. We discuss innovative applications across different malignancies, including targeted delivery of tyrosine kinase inhibitors in chronic myeloid leukemia, small interfering RNA delivery in lymphoma, and proteasome inhibitor transport in multiple myeloma. Notably, engineered exosomes demonstrate remarkable efficacy in overcoming drug resistance mechanisms and enhancing therapeutic outcomes while minimizing adverse effects. Surface modification techniques, including antibody decoration and peptide conjugation, have significantly improved targeting specificity and cellular uptake. Despite promising results, challenges persist in scalable production, standardization, and regulatory compliance. We analyze current limitations and propose future directions, emphasizing the development of standardized protocols, quality metrics, and regulatory frameworks. As this field advances, engineered exosomes show the potential to revolutionize hematological cancer treatment through precise, personalized therapeutic delivery systems with enhanced efficacy and reduced toxicity.