IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25+CD8+ T cells

A multi-organ map of the human immune system across age, sex and ethnicity

“…Genes that were most consistently differentially transcribed included several immunotherapy targets. IL2 is targeted in immunotherapy, particularly in the treatment of certain cancers like melanoma and renal cell carcinoma 44 ; the immune genes TNFSF4, important in T cell activation 45 , have been proposed as immunotherapy targets, and GNLY, important in NK cell biology, is a diagnostic marker and have potential as immunotherapy target 46…”

“…Importantly, we show that sexual dimorphism can have practical clinical implications, with some of the most differential genes across tissues and cell types being established or proposed immunotherapy targets, such as IL2 44 ; TNFSF4 45 , and diagnostic markers, such as GNLY 46 .…”

“…Genes that were most consistently differentially transcribed included several immunotherapy targets. IL2 is targeted in immunotherapy, particularly in the treatment of certain cancers like melanoma and renal cell carcinoma 44 ; the immune genes TNFSF4, important in T cell activation 45 , have been proposed as immunotherapy targets, and GNLY, important in NK cell biology, is a diagnostic marker and have potential as immunotherapy target 46 Our results resolve the tissue and cell-type specificity of sex-related immune differences, ranking naive B cells and granulocytes as most consistently affected across tissue and immunotherapy gene targets among the most affected overall. The dot size represents significance probability; the bigger, the higher, the lower the FDR.…”

Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma

“…36,38,57 Furthermore, development of IL-2-like molecules with prolonged half-life or selective affinity for effector T cells is ongoing, possibly enabling lower dosages and reduced dose frequency while retaining efficacy. 58,59 Promising research was published regarding ANV419, a highly selective IL-2Rβγ-binding agonist, inducing the proliferation of CD8 + T cells and natural killer cells instead of regulatory T cells. 60 Another ongoing clinical trial investigates whether membrane-bound IL-15 could be a viable treatment option, replacing the need for IL-2 administrations after TIL infusion (NCT05470283).…”

“…Strategy 2: Another possibility to reduce toxicity is to decrease the IL-2 dosage frequency, as no studies have shown a correlation between the number of IL-2 boluses and outcome 36,38,57 . Furthermore, development of IL-2–like molecules with prolonged half-life or selective affinity for effector T cells is ongoing, possibly enabling lower dosages and reduced dose frequency while retaining efficacy 58,59 . Promising research was published regarding ANV419, a highly selective IL-2Rβγ-binding agonist, inducing the proliferation of CD8 + T cells and natural killer cells instead of regulatory T cells 60 .…”