NKG2C

SEATTLE--( BUSINESS WIRE )--Combined, infection, autoimmunity and cancer account for four out of every 10 deaths worldwide, and represent major global health challenges. In a just-published paper in the journal Cell Reports , Institute for Systems Biology (ISB) researchers highlight a novel discovery of how the human immune system works in common ways across diseases, and offer promising avenues for exploring multi-disease therapeutic strategies. Many therapies, while effective for one class of disease, may aggravate others. Cancer treatments like immune checkpoint blockade, for example, can trigger autoimmunity. Similarly, drugs targeting autoimmune diseases may leave patients more susceptible to infections and cancer. “Understanding shared human immune system characteristics across these disease contexts is crucial for identifying potential therapeutic strategies that could treat a patient’s primary ailment while not triggering secondary conditions,” said ISB President Dr. Jim Heath, corresponding author of the paper. To address these challenges, ISB researchers have identified two immune cell receptors – NKG2A and NKG2C – as factors influencing immune responses across diseases. These receptors, which are not seen together on the same cells, have gained significant interest in the immunology community for their ability to regulate the function of T cells and natural killer cells. The research team examined deep clinical and biological data of 526 patients with infection, 162 patients with lupus, and 11,180 patients with cancer, considering whether the patients’ T cells or natural killer immune cells could be classified as NKG2A biased or NKG2C biased. Through a comprehensive analysis, they found that an NKG2A-dominant immune response correlates with decreased disease severity and mortality, and lower prevalence of post-acute chronic conditions across all disease contexts. “Patients with more NKG2A activity showed decreased inflammation and increased survival rates across different disease contexts, including viral infections, autoimmune diseases like lupus, and various cancer types,” said Daniel Chen, first author of the paper. The study also identified distinct immune cell profiles associated with NKG2A and NKG2C biases, which could lead to potential therapeutic targets for modifying immune responses across diseases. It also suggests that treating NKG2A as a drug target for cancer immunotherapy, which is an idea that has been pursued in oncology clinical trials, would likely not be successful. The study’s findings are, in fact, consistent with what has been found in those trials. “We plan future studies to delve deeper into the biological mechanisms underlying these immune biases, which we believe will lead to developing more targeted and effective treatments,” Heath said. About ISB Institute for Systems Biology (ISB) is a collaborative and cross-disciplinary non-profit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, COVID-19, as well as many infectious diseases. Our science is translational, and we champion sound scientific research that results in real-world clinical impacts. ISB is an affiliate of Providence, one of the largest not-for-profit health care systems in the United States. Follow us online at isbscience.org , and on YouTube , Facebook , LinkedIn , X (formerly Twitter) and Instagram .

SHANGHAI & SUZHOU, China & GERMANTOWN, Md.--(BUSINESS WIRE)-- Elpiscience Biopharmaceuticals, Inc. (“Elpiscience”), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, presented studies for its innovative immunotherapeutic molecules at the SITC 2023 Annual Meeting, including KG2A/NKG2C dual-targeting antibody ES015-2, a high affinity LILRB1 specific blocking antibody ES008-a, and the first-in-class anti-CD39/TGF-βRII bifunctional fusion protein ES014. Study Highlights: Title: Selective delivery of TGFβ “trap” to CD39-expressing immune and stroma cells reshapes tumor microenvironment and rejuvenates antitumor immunity Abstract Number: 453 CD39-Adenosine and TGFβ are two key immune suppressive pathways within the tumor microenvironment (TME). TGFβ, in contrast to its biphasic effects on tumor cells, acts on stromal cells and immune cells in the TME, which commonly express high levels of CD39, to promote tumor progression. CD39-targeted TGFβ “trap” is thus more likely to effectively inhibit tumor progression. Our study showed that ES014, a bifunctional antibody–ligand trap which comprises an antibody targeting CD39 fused to a TGFβ receptor II ectodomain, can inhibit TGFβ activity and lead to cancer killing in ex vivo models. A phase I clinical study is ongoing to primarily investigate the safety, tolerability, and preliminary clinical activity of ES014 in patients with advanced solid tumors. Highlights: ES014 binds and neutralizes both CD39 and TGFβ. ES014 promoted killing of tumors from NSCLC patients in ex vivo MPE model. ES014 inhibits Treg differentiation and TGFβ-induced CD39 expression on T cells. ES014 promotes T cell survival. Title: ES015-2, a first-in-class NKG2A and NKG2C dual-targeting antibody, demonstrated potent anti-tumor immune response Abstract Number: 498 The inhibitory receptor NKG2A and the activating receptor NKG2C modulate the function of NK and CD8 T cells by recognizing the same ligand HLA-E. NKG2A is selectively expressed on lymphocytes with cytolytic function, and the NKG2C “engager” has the potential to generate a strong antitumor response against various tumors. Inhibiting NKG2A and HLA-E alone was not as effective as had been expected in both mouse tumor models and in clinical trials. Our NKG2A/NKG2C dual targeting antibody ES015-2 can inhibit NKG2A function yet promoting NKG2C action, leading to superior anti-tumor response. Highlights: ES015-2 is a NKG2A/NKG2C dual targeting antibody. ES015-2 can completely block the interaction of NKG2A/CD94 with HLA-E, thereby inhibits HLA-E-induced NKG2A inhibitory signaling. Ligation of ES015-2 effectively potentiates the activation of NKG2C+ NK cells and T cells. Title: ES008-a, a high affinity LILRB1 specific blocking antibody activates multiple immune cells to fight cancers Abstract Number: 510 LILRB1 is the most broadly expressed member of LILRB family on various immune cells. Blocking LILRB1 augments macrophage phagocytosis of tumor cells, restores cytotoxic function of NK cells, and enhances tumor cell killing by effector CD8+ T cells. The high affinity LILRB1 specific blocking antibody ES008-a can activate multiple immune cells to fight cancers. Highlights: ES008-a is a high affinity LILRB1-specific blocker that can completely block HLA-G/LILRB1 and HLA-A2/LILRB1 interactions. ES008-a promotes NK cell-mediated destruction of tumor cells. ES008-a synergizes with CD47/SIRPα inhibitors in enhancing macrophage phagocytosis of tumor cells. About Elpiscience Elpiscience is a clinical-stage biopharmaceutical company dedicated to developing life-changing immuno-oncology therapies for cancer patients worldwide. The company’s innovative approach is focused on removing immunosuppressive factors in the tumor microenvironment, by targeting the adenosine pathway and myeloid checkpoints. A pipeline of novel molecules has been developed using its proprietary platforms including a powerful Bispecific Macrophage Engager (BiME®) technology that connects and activates macrophages for solid tumor killing without causing cytokine storms. For more information, please visit: View source version on businesswire.com: Contacts BD inquiries: BD@elpiscience.com Media inquiries: PR@elpiscience.com Source: Elpiscience Biopharmaceuticals, Inc. View this news release online at:

SHANGHAI & SUZHOU, China & GERMANTOWN, Md.--(BUSINESS WIRE)-- Elpiscience Biopharma, Inc. (“Elpiscience”), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, today announced it will have three poster presentations at the SITC 2023 Annual Meeting taking place November 3-5, 2023, in San Diego. The posters will highlight its studies on three innovative molecules including a first-in-class NKG2A/NKG2C dual-targeting antibody ES015, a high affinity LILRB1 specific blocking antibody ES008-a, and the first-in-class anti-CD39/TGF-βRII bifunctional fusion protein ES014 which has been proven to be able to deliver TGFβ “trap” to CD39-expressing immune and stroma cells to reshape tumor microenvironment and rejuvenates antitumor immunity. Poster presentation details: Title: Selective delivery of TGFβ “trap” to CD39-expressing immune and stroma cells reshapes tumor microenvironment and rejuvenates antitumor immunity Abstract Number: 453 Date and time: November 3, 2023; 9 am –7 pm PDT Location: Exhibit Halls A and B1 – San Diego Convention Center Title: ES015, a first-in-class NKG2A and NKG2C dual-targeting antibody, demonstrated potent anti-tumor immune response Abstract Number: 498 Date and time: November 4, 2023; 9 am –8:30 pm PDT Location: Exhibit Halls A and B1 – San Diego Convention Center Title: ES008-a, a high affinity LILRB1 specific blocking antibody activates multiple immune cells to fight cancers Abstract Number: 510 Date and time: November 4, 2023; 9 am –8:30 pm PDT Location: Exhibit Halls A and B1 – San Diego Convention Center About Elpiscience Elpiscience is a clinical-stage biopharmaceutical company dedicated to developing life-changing immuno-oncology therapies for cancer patients worldwide. The company’s innovative approach is focused on removing immunosuppressive factors in the tumor microenvironment, by targeting the adenosine pathway and myeloid checkpoints. A pipeline of novel molecules has been developed using its proprietary platforms including a powerful Bispecific Macrophage Engager (BiME®) technology that connects and activates macrophages for solid tumor killing without causing cytokine storms. For more information, please visit: