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In situ immunization of a TLR9 agonist virus-like particle enhances anti-PD1 therapy

CMP-001 is a novel Toll-like receptor-9 agonist that consists of an unmethylated CpG-A motif-rich G10 oligodeoxynucleotide (ODN) encapsulated in virus-like particles. In situ vaccination of CMP-001 is believed to activate local tumor-associated plasmacytoid dendritic cells (pDCs) leading to...

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Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors

MEDI9197 is an intratumorally administered toll-like receptor 7 and 8 agonist. In mice, MEDI9197 modulated antitumor immune responses, inhibited tumor growth and increased survival. This first-time-in-human, phase 1 study evaluated MEDI9197 with or without the programmed cell death ligand-1 (PD...

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SITC Cancer Immunotherapy Guidelines - Multiple Myeloma - Recorded Webinar and Presentation Slides

On September 3, 2020, leading experts in cancer immunotherapy presented an overview of the publication "The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma" during a live webinar. The recorded webinar and presentation slides are...

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First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers

E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics,...

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Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1

The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells ...

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Heat shock and HSP70 regulate 5-FU-mediated caspase-1 activation in myeloid-derived suppressor cells and tumor growth in mice

The authors have previously shown that 5-fluorouracil (5-FU) selectively kills myeloid-derived suppressor cells (MDSCs) and activates NLRP3 (NOD-leucine rich repeat and pyrin containing protein 3) inflammasome. NLRP3 activation leads to caspase-1 activation and production of IL-1β, which in turn...

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CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma

Patients with BRCA1-associated protein 1 (BAP1)-mutant clear cell renal cell carcinoma (ccRCC) have worse prognosis. C-C chemokine receptor 5 (CCR5) plays an important role in ccRCC development and its expression is elevated in BAP1-mutant tumors. The authors conclude that CCR5 in BAP1-mutant...

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C reactive protein impairs adaptive immunity in immune cells of patients with melanoma

High C reactive protein (CRP) levels have been reported to be associated with a poor clinical outcome in a number of malignancies and with programmed cell death protein 1 immune checkpoint blockade in patients with advanced cancer. Little is known about the direct effects of CRP on adaptive...

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Lifting the innate immune barriers to antitumor immunity

The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response....