Efficient combination of radiotherapy and CAR-T - A systematic review.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.

The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience.

The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients.

CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase.

BACKGROUND: Chronic myeloid leukemia (CML) biology seemed to be perfectly explored especially at the beginning of the tyrosine kinase inhibitors era. Later years with imatinib and second-generation tyrosine kinase inhibitors showed a variety of resistance mechanisms and it became obvious that the bcr-abl chimeric gene is not the only enemy to fight. Some studies assumed the decreased rate of programmed cell death (apoptotic) to be the primary mechanism by which BCR-ABL affects expansion of the leukemic clone in CML. Therefore, the aim of this study was to investigate the role of c-kit inhibition in treatment response. METHODS: Cytogenetic analysis, real-time quantitative reverse-transcriptase polymerase chain reaction, flow-cytometric analysis and imatinib serum level quantification were applied. RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. The fraction of apoptotic CD34+CD117+ cells in this patient group was significantly higher than in nonresponders. CONCLUSION: To achieve optimal treatment response in CML patients, the elimination of CD34+CD117+ may be necessary through an apoptotic pathway.