Resumen de: AU2025203054A1
The disclosure provides cells comprising CD19-directed chimeric antigen receptor (CAR) genetically modified autologous T cell immunotherapy for the treatment of, e.g., relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Some aspects of the disclosure relate to methods of treatment and monitoring following infusion of T cell therapy provided herein.
Resumen de: WO2025106552A1
Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric receptors and various dosing regimens for administering such cells. In several embodiments, the immune cells express a chimeric receptor that targets ligands of NKG2D. In several embodiments, the cancer is a leukemia, such as acute myeloid leukemia (AML).
Resumen de: WO2025106732A1
Single-nucleotide variants (SNVs) in key T cell genes can drive clinical pathologies and could be repurposed to improve cellular cancer immunotherapies. Here, we perform massively parallel base editing screens to generate thousands of variants at gene loci annotated with known or potential clinical significance. We discover a broad landscape of putative gain- (GOF) and loss-of-function (LOF) mutations, including in PIK3CD and its regulatory subunit PIK3R1, LCK, SOS, AKT1, and RHOA. Base editing of PIK3CD and PIK3R1 variants in T cells with an engineered T cell receptor specific against a melanoma epitope or in different generations of CD19 chimeric antigen receptor T (CAR-T) cells demonstrates that discovered GOF variants, but not LOF or silent mutation controls, enhanced signaling, cytokine production and lysis of cognate melanoma and leukemia cell models, respectively. Additionally, we show that generations of CD19 CAR-T cells engineered with PIK3CD GOF mutations demonstrate enhanced antigen-specific signaling, cytokine production, and leukemia cell killing, including when benchmarked against other recent strategies.
Nº publicación: WO2025106485A1 22/05/2025
Solicitante:
KYMERA THERAPEUTICS INC [US]
ALBERT EINSTEIN COLLEGE MEDICINE [US]
KYMERA THERAPEUTICS, INC,
ALBERT EINSTEIN COLLEGE OF MEDICINE
Resumen de: WO2025106485A1
The present invention relates to STAT3 degraders and methods of use thereof for treating leukemia.