Mehrnaz Safaee Talkhoncheh’s Post

A big shout-out to all the collaborators on the publication of our work in Cancer Research on ATG-101, a bispecific Ab that targets PD-L1 and 41BB. It is a nice demonstration of the use of modeling in integrating preclinical in vitro and in vivo data to predict human efficacious dose by finding the sweet spot between maximal trimer formation and PD-L1 receptor occupancy. https://lnkd.in/ePbkBvV8 #mechanisticmodeling #PKPD #bispecific

Tertiary lymphoid structures (TLS) are lymph node-like organizations of immune cells within inflamed tissues that can drive immune cell activation. TLS has been a hot topic in the field of immuno-oncology, where it is believed they play a critical role in influencing the tumor microenvironment. Since TLSs are associated with improvement in clinical outcomes, their presence or induction following cancer therapies could be a valuable predictor of therapeutic responses. Stop by our blog to find out how our team studies tertiary lymphoid structures – a promising biomarker for immunotherapy. https://bit.ly/3FmiS6O #TertiaryLymphoidStructures #Biomarker #Immunotherapy #SpatialBiology

The illustration below delves into the mechanisms of immunogenic cell death. Several danger signaling molecules are involved in this process, induced by oxaliplatin and likely paclitaxel. Hyperthermia also influences the induction of danger-associated molecular patterns (DAMPs), such as ▶ Heat Shock Proteins (HSPs) ▶ HMGB1 ▶ Surface Calreticulin (CRT) ▶ ATP release These DAMPs are crucial for initiating immunogenic cell death, leading to a cascade of immune activation and tumor-specific cell death. At ElmediX, we are dedicated to further exploring hyperthermia and its mechanisms, leveraging these insights to develop more effective cancer therapies. 👉🏻 More info on www.elmedix.com #cancerresearch #elmedix #hyperthermia

Exploring ER Stress: From Cellular Balance to Cancer – New Therapeutic Insights APRIL 1, 2024 Jeya Chelliah B.Vsc Ph.D. The endoplasmic reticulum (ER) is a central hub of cellular activity, responsible for critical processes such as protein folding, lipid synthesis, and calcium storage and signaling. This multifunctional organelle plays a pivotal role in maintaining cellular health and integrity. However, under conditions of stress, the ER can become a double-edged sword, contributing to the initiation and progression of cancer. This blog post delves into the complex nature of the ER, exploring how its dysfunction can lead to oncogenesis and how these mechanisms offer potential targets for therapeutic intervention. https://lnkd.in/eka3wKJV

#Researchers, FMS-like tyrosine kinase 3 (FLT3) is expressed on myeloid, lymphoid, and dendritic cell progenitors. Its natural activator, the FLT3 ligand (FL), acts as a cytokine and an important regulator of hematopoiesis. Upon binding, FLT3 is rapidly activated and internalized. With BI-3404, we now share a FL-mimicking humanized antibody on hashtag #opnMe. We invite scientists to submit collaboration proposals that demonstrate a new role of FLT3 activation in disease indications beyond cancer. Learn more: https://lnkd.in/eJQVkJ9S

This is interesting: Lowering Fecal Immunochemical Test Positivity Threshold vs Multitarget Stool RNA Testing for Colorectal Cancer Screening https://lnkd.in/dgJPcEx2 This publication found that FIT (the fecal immunochemical test), the cheapest colorectal screening test, is very powerful. By lowering the cut-off level (positivity threshold), FIT demonstrated sensitivities of 94.9% for cancer and 44.7% for advanced adenoma at 86.9% specificity. These are very high numbers. The FDA's required minimum specificity is 90%, but very probably at that level the FIT test is still outstanding. A FIT reagent costs around $1. #CancerScreening #09

#MMAE #ADC #ADCPayload #ADCLinker #Peptides #PeptideLinker In this article, it displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression. MMAE is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) to treat several different cancer types. If need MMAE, please come to me by zhuyujiao@chemexpress.com. Thanks.

✨ #Cancer #Cell: Discovery of the first #clinical KRAS G12D inhibitor, HRS-4642 📣 #HRS4642 is a high affinity, selective, longacting, and non-covalent #KRAS G12D inhibitor, which has demonstrated robust efficacy against KRAS G12Dmutant cancers both in #vitro and in #vivo. Genomewide CRISPR-Cas9 screening has elucidated the sensitization and resistance spectrum of HRS-4642 and firstly revealed that the proteasome inhibitor, carfilzomib, acts synergistically as a sensitizing agent. Additionally, HRS-4642 therapy, especially combined with #carfilzomib, effectively remodels the tumor microenvironment toward a more immune-permissive state. Given the compelling potency and selectivity, HRS-4642 is one of the first of its kind to advance to clinical trials (#NCT05533463). In the recruitment of 9 patients with #NSCLC, HRS-4642 led to objective partial response in two patients and stable disease in seven patients. 👉 #MCE Raleted #Products: https://lnkd.in/gG7iE8P4 👉 For more detailed information: https://lnkd.in/eKtw_nhB

New!📌 Validation of a multiomic model of #plasmaextracellularvesicle PD-L1 and radiomics for prediction of response to #immunotherapy in NSCLC ----------------------------- Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. Here Christian Rolfo, MD, PhD, MBA,Dr.h.c. et al. showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs. Look here⤵️ https://lnkd.in/dbEeYh6y #LungCancer #Immunecheckpointinhibitor #LiquidBiopsy IFO - Istituto Nazionale Tumori Regina Elena - Istituto Dermatologico San Gallicano

Evitria’s journal club - paper of the week 49 Potent Fc Receptor Signaling by IgA Leads to Superior Killing of Cancer Cells by Neutrophils Compared to IgG by Arianne Brandsma et al (2019) https://lnkd.in/eBsSJupJ While all approved therapeutic mAbs use the IgG format, there is a growing interest in using alternative classes and subtypes to harness new modes of therapeutic action. This paper explores the activation of neutrophils by IgA for cancer cell killing, and features one of our favorite videos to explain the difference. If you would like to reformat your antibody, get in touch with evitria to learn how our modular cloning and production system enables you to explore different modes of action: https://lnkd.in/eB4mcxN #antibodies  #antibodytherapeutics #antibodyengineering