Publications by authors named "J R Lasarte"

Article Synopsis
  • Glypican-3 (GPC3) is a potential target for T-cell therapy in hepatocellular carcinoma (HCC), but current CAR T-cell approaches face issues like low persistence and GPC3 shedding.
  • Researchers immunized HLA-A2 transgenic mice to find GPC3-specific T-cell receptors (TCRs) and engineered human T cells (TCR-Ts) that effectively recognize GPC3-positive HCC cells.
  • TCR-B-T cells showed superior effectiveness compared to traditional CAR T-cells, and combining CAR-T and TCR-B-T cells may enhance therapeutic results in treating HCC.
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Article Synopsis
  • - The complexities of the tumor microenvironment (TME), particularly the role of regulatory T cells (Treg), complicate the effectiveness of cancer immunotherapies by allowing tumors to evade the immune system.
  • - Researchers are exploring methods to inhibit Treg, which are important for immune balance but can hinder cancer treatment when present in tumors, using mechanistic mathematical models to simulate and predict outcomes of various therapies.
  • - The review discusses various computational models that analyze Treg's impact on immunotherapy failure, highlights molecules associated with immune suppression in the TME, and presents potential new therapies targeting Treg for effective treatment combinations.
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Immunostimulatory cytokines and immune checkpoint inhibitors hold promise as cancer therapeutics; however, their use is often limited by reduced efficacy and significant toxicity. In this study, we developed small-format immunocytokines (ICKs) based on interleukin-12 (IL-12) and blocking nanobodies (Nbs) targeting mouse and human programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1). Both PD-1- and PD-L1-targeted ICKs demonstrated similar in vitro performance, significantly increasing IL-12 tethering to immune cells and enhancing T cell cytotoxic activity compared with IL-12 alone.

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P60, a Foxp3 inhibitory peptide, can hinder the regulatory T cell (Treg) activity and impair tumor proliferation. However, low systemic stability and poor specificity have led to daily dosing to achieve therapeutic effect. Therefore, this study aims to improve P60 stability and specific delivery through its encapsulation in liposomes targeting CD25, constitutively expressed in Tregs.

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