PRAME-Targeted T Cells Clear Metastatic Pediatric Tumor
A personalized T-cell receptor therapy has produced a complete response in an adolescent with advanced, treatment-resistant nephroblastoma.
The 17-year-old patient had experienced repeated relapses over ten years and had tumors in the abdomen, lungs, liver, pelvis, and brain. Molecular profiling identified expression of PRAME, a tumor antigen already being investigated as an immunotherapy target in adults.
The autologous T-cell therapy was manufactured locally in seven days. The patient’s cells were genetically modified using a vector supplied by Immatics to express a T-cell receptor that recognizes PRAME. Nine days after infusion, a biopsy showed extensive T-cell infiltration and tumor-cell death.
Three months after treatment, no viable tumor cells were detected, while imaging and blood tests showed no evidence of active cancer almost one year after infusion. A Phase I/II trial involving up to 18 children and adolescents with PRAME-positive solid tumors is planned for 2027. Source
CAR T Cells Remain Active a Decade After Treatment
CD19-directed CAR T cells can remain functionally active for up to ten years in patients treated for B-cell non-Hodgkin lymphomas, according to a study published in Nature Medicine.
Researchers analyzed longitudinal samples from 38 patients who received the autologous CAR T-cell therapy now known as tisagenlecleucel. After more than ten years of follow-up, no relapses occurred beyond 5.4 years. Ten-year lymphoma-free survival was 32 percent for large B-cell lymphoma and 47 percent for follicular lymphoma.
Among eight long-term responders with suitable samples, CAR T cells remained detectable more than five years after treatment in five patients. Detailed analysis of one patient at 9.3 years identified a dominant population of CD4-negative and CD8-negative CAR T cells with an activated, effector-memory-like phenotype. Source
In Vivo CRISPR Screen Identifies Stronger CAR T Cells
Researchers have developed an in vivo genome-wide CRISPR screening platform to identify gene edits that could improve CAR T-cell activity against solid tumors.
The platform allowed the effects of almost 20,000 gene knockouts to be evaluated in human T cells inside tumors in mice. Previous genome-wide screens largely relied on cell-culture models that do not reproduce the suppressive conditions encountered within a living tumor.
Knocking out P2RY8 increased T-cell infiltration into tumors, while removing GNAS helped the cells resist suppressive signals and maintain interferon-gamma production. Combining both edits produced the strongest effect: two-thirds of mice in a lung cancer model remained tumor-free after receiving a low dose of the edited cells, compared with none given control-edited cells.
The edited cells also showed activity in models of melanoma, pancreatic cancer, gastroesophageal adenocarcinoma, and uterine sarcoma, as well as when manufactured from patient-derived T cells. Source
Genetic Recorder Exposes CAR T-Resistant Tumor Cells
A genetically encoded recording system could help identify and target soft, stem-like cancer cells that resist CAR T-cell therapy.
Researchers found that softer tumor cells displayed increased calcium signaling and were more likely to acquire stem-cell-like characteristics associated with treatment resistance. They developed a “Mechano-Recorder” that converts this transient signaling into a persistent fluorescent marker, creating a record of the mechanical environment experienced by each cell.
The team then replaced the fluorescent marker with CD19, causing soft tumor cells to display an antigen recognized by CD19-directed CAR T cells. In breast cancer cell lines, patient-derived cells, and mouse models, this approach increased T-cell infiltration and tumor-cell killing.
The strategy has also been tested in models of glioblastoma, pancreatic cancer, and prostate cancer. Source
Hemogenyx Advances CAR T Manufacturing in Estonia
Hemogenyx Pharmaceuticals has entered a definitive agreement with Cellin Technologies covering the manufacture and clinical implementation of its HG-CT-1 CAR T-cell therapy in Estonia.
HG-CT-1 is an autologous, FLT3-directed CAR T-cell therapy in Phase I development for relapsed or refractory acute myeloid leukemia. The agreement establishes Cellin as Hemogenyx’s exclusive manufacturing and operational partner in Estonia for five years.
Hemogenyx will transfer its manufacturing process to Cellin’s GMP facility in Tallinn. Cellin will then prepare an application to supply the therapy through Estonia’s hospital exemption pathway, which permits certain unauthorized advanced therapy medicinal products to be prepared on a non-routine basis for individual patients. Source
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