synthetic miR-142 / TGen, City of Hope - LARVOL DELTA

Acquired microRNA-142 Deficit Drives Escape Mechanisms of Anti-Leukemic Surveillance during Blast Crisis Transformation of Chronic Myeloid Leukemia (CML) (ASH 2023) - "To correct miR-142 deficit, we produced a synthetic miR-142 mimic oligonucleotide (CpG-M-miR-142)...The mice treated with TKI+CpG-M-miR-142 (median survival: 107 days, p=0.001) or TKI+PD-1 inhibitor (104 days, p=0.002) survived longer than the controls treated with TKI alone (66 days); the triplet combination (TKI+CpG-M-miR-142+PD-1 inhibitor) is expected to improve survival further (ongoing experiment). In summary, CpG-M-miR-142 alone and in combination with TKI or PD-1 inhibitor rescued T-cell antileukemic activity and prolonged survival in BC CML murine and PDX models, thereby providing a potentially new therapeutic approach for BC CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CD34 • KIT • MIR142

MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia. (PubMed, J Hematol Oncol) - "We have identified a potentially novel strategy to enhance CAR-T cell persistence and efficacy in AML by counteracting a leukemia-induced, microRNA-deficiency mediated mechanism of immune suppression."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL1RAP • MIR142

Acquired microRNA (miR)-142 Deficit Drives Immune Escape in Acute Myeloid Leukemia (AML) (ASH 2024) - "Next, to test if restoring miR-142 improves T cell control of leukemia growth, we treated a cohort of MllPTD/WTFlt3ITDITD AML mice with M-miR-142 (a synthetic miR-142) or scrambled control (SCR) for 3 weeks...Recipients of M-miR-142-treated donor BM also lived significantly longer than recipients of SCR-treated donor BM (median : 92 vs 21 days, p<0.0001). We concluded that T-miR-142 deficit is acquired during AML progression, causing decreased antileukemic surveillance and contributing to disease growth, which can be rescued by M-miR-142."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • IL6 • KIT • MIR142 • PD-1

City of Hope and TGen Research Reveals What Potentially Causes a Leukemia to Become More Aggressive (Businesswire) - "The team developed a synthetic version of miR-142 and tested it in mouse models of BP CML. They found that adding miR-142 prevented CML transformation and some mice with BP CML were even cured of their disease....Researchers also found that adding tyrosine kinase inhibitors, which is a Food and Drug Administration-approved therapy for CML, increased the anti-leukemic activity of the synthetic miR-142."

Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Oncology