25 research outputs found
P06.06 Enhancing trafficking and resistance to immunosuppression of synthetic agonistic receptor-transduced T cells in solid tumor models
n/
Factors associated with the designation of a health care proxy and writing advance directives for patients suffering from haematological malignancies
Surface Modification of Fine Powders by Atmospheric Pressure Plasma in a Circulating Fluidized Bed Reactor
Determination of boron and hydrogen in materials for multicrystalline solar cell production with prompt gamma activation analysis
Characterization of bispecific antibodies that drive synthetic agonistic receptor - transduced T cells to mediate specific and conditional therapy in human pancreatic cancer models.
Combined tumor-directed recruitment and protection from immune suppression enable CAR T cell efficacy in solid tumors.
CAR T cell therapy remains ineffective in solid tumors, due largely to poor infiltration and T cell suppression at the tumor site. T regulatory (Treg) cells suppress the immune response via inhibitory factors such as transforming growth factor–β (TGF-β). Treg cells expressing the C-C chemokine receptor 8 (CCR8) have been associated with poor prognosis in solid tumors. We postulated that CCR8 could be exploited to redirect effector T cells to the tumor site while a dominant-negative TGF-β receptor 2 (DNR) can simultaneously shield them from TGF-β. We identified that CCL1 from activated T cells potentiates a feedback loop for CCR8+ T cell recruitment to the tumor site. This sustained and improved infiltration of engineered T cells synergized with TGF-β shielding for improved therapeutic efficacy. Our results demonstrate that addition of CCR8 and DNR into CAR T cells can render them effective in solid tumors