By: Kerri Fitzgerald
Researchers conducted a proof-of-concept study for genetically redirecting T cells, offering a potential immunotherapy target for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), conditions for which immunotherapy options have lagged compared with other hematologic malignancies.
The findings were published in Cell by Won Jun Kim, BS, of Memorial Sloan Kettering Cancer Center (MSKCC), and colleagues. The study was conducted as a collaboration between researchers from MSKCC and Fred Hutchinson Cancer Center.
The researchers determined that certain mutations (eg, SF3B1, SRSF2, U2AF1, and ZRSR2) found in nearly 70% of patients with MDS and nearly 33% with AML cause errors in RNA splicing and lead to cancer formation and growth.
The used samples from MSKCC patients treated for AML and MDS to determine defective neoantigens that could be a targeted via immunotherapy.
They used a T-cell receptor (TCR) gene therapy technique, similar to chimeric antigen receptor T-cell therapy, and found that mice treated with TCR therapy experienced a significant tumor reduction and had longer survival than those not treated with TCR therapy.
Further research is needed to determine a potential role of TCR treatment for MDS and AML in a human population.
Reference
Kim WJ, Crosse EI, De Neef E, et al. Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias. Cell. 2025:S0092-8674(25)00399-X. doi:10.1016/j.cell.2025.03.047
