Advanced Biotech Research Techniques

Researchers at Johns Hopkins University have created a revolutionary protein “switch” that tricks cancer cells into manufacturing their own chemotherapy drugs, causing them to self-destruct while sparing healthy cells. Instead of delivering drugs directly to cancer cells, this method uses a harmless “prodrug” that only becomes activated inside cancer cells when the switch detects specific cancer markers. The switch is made by combining two proteins: one that senses cancer markers and another from yeast that converts the inactive prodrug into a potent cancer-killing drug. When the switch detects cancer, it activates the drug inside that cell, turning the cancer cell into a drug factory that destroys itself. To work, the switch must enter cancer cells either by delivering the protein itself or by inserting the gene that makes the protein, allowing the cancer cell’s own machinery to produce the switch. Afterward, patients receive the inactive chemotherapy prodrug, which becomes activated only inside cancer cells. This new approach focuses on producing the drug inside cancer cells rather than just delivering it to them, which could kill more cancer cells while reducing harmful side effects on healthy tissue. Lab tests on human colon and breast cancer cells have shown promise, and animal testing is expected to start within a year. While still early, this technique offers a radically different way to attack cancer. #PNAS #RMScienceTechInvest

Why do brain metastases resist immunotherapy—even when the same cancer responds outside the brain? 🧠💥 Excited to share our new study answering this question—led by an amazing former PhD student, Dr. Vladimir Wischnewski 🎉 We set out to ask if combining stereotactic radiosurgery (SRS) with immune checkpoint blockade (anti-PD1) can enhance immune responses in breast cancer-brain metastases (BrM)? We found that while CD8+ T cells infiltrate BrM, they are functionally suppressed—even when activated. In contrast, the same cancer cells growing in the mammary fat pad – modelling a primary breast tumor – respond robustly to the same combination therapy. Using a panel of in vivo and ex vivo strategies, we identified Trem2+ macrophages and neutrophils as key players in suppressing T cell function specifically in the brain tumor microenvironment. Why is this important? BrM remains a major challenge in breast cancer, with limited therapeutic options. Our study provides insight into the local immunosuppressive mechanisms that block otherwise effective immunotherapies in the brain—highlighting new cellular targets to potentially overcome this resistance. 📄 Full open-access paper: https://lnkd.in/efJ9b-j9 Warmest congratulations to Vlad for leading this major body of work during his PhD 🤩, and to all the wonderful co-authors from my lab who contributed to this #CellReports publication – Paola Guerrero Aruffo, Matteo Massara, Klara Soukup, Roeltje Maas 👏👏, and many thanks to everyone from the core facilities who also supported us at the Agora Cancer Center and the Faculty of Biology and Medicine of UNIL 🙏 Finally, we are very grateful to the Breast Cancer Research Foundation, Swiss National Science Foundation (Advanced Grant TMAG-3_209224), Fondation ISREC, Ludwig Institute for Cancer Research, and the University of Lausanne for their generous funding support. #BrainMetastasis #ImmunotherapyResistance #TumorMicroenvironment #CancerResearch #Radiotherapy #SingleCell #BreastCancer

What if the 𝐯𝐞𝐫𝐲 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐦𝐞𝐚𝐧𝐭 𝐭𝐨 𝐟𝐢𝐠𝐡𝐭 𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐢𝐨𝐧 in your body is actually helping cervical cancer cells 𝐬𝐮𝐫𝐯𝐢𝐯𝐞 𝐫𝐚𝐝𝐢𝐚𝐭𝐢𝐨𝐧 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭? Recent groundbreaking research by Hu et al. (2025) has uncovered something that changes what we thought we knew about cervical cancer radiotherapy resistance. 𝐂𝐗𝐂𝐋𝟖, a protein our bodies produce to manage inflammation, is actually acting as a shield for cancer cells during radiation treatment. Scientists spent nearly a year creating 𝐫𝐚𝐝𝐢𝐨𝐭𝐡𝐞𝐫𝐚𝐩𝐲-𝐫𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐭 𝐜𝐞𝐫𝐯𝐢𝐜𝐚𝐥 𝐜𝐚𝐧𝐜𝐞𝐫 𝐜𝐞𝐥𝐥 lines that mimic what happens in real patients. 𝐖𝐡𝐚𝐭 𝐭𝐡𝐞𝐲 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐞𝐝 𝐰𝐚𝐬 𝐞𝐱𝐭𝐫𝐚𝐨𝐫𝐝𝐢𝐧𝐚𝐫𝐲 - CXCL8 was among the top genes helping these cells survive radiation doses that should have eliminated them. When researchers knocked down CXCL8 in resistant cells, something remarkable happened. The cells became vulnerable to radiation again. They stopped proliferating, formed fewer colonies, and became more susceptible to treatment-induced cell death. The flip side was equally revealing. When they added CXCL8 to normal cervical cancer cells, these cells developed resistance to radiation therapy. This matters because cervical cancer radiotherapy has remained frustratingly limited, with 𝟓-𝐲𝐞𝐚𝐫 𝐬𝐮𝐫𝐯𝐢𝐯𝐚𝐥 𝐫𝐚𝐭𝐞𝐬 ranging from 𝟐𝟎-𝟔𝟓% 𝐟𝐨𝐫 𝐚𝐝𝐯𝐚𝐧𝐜𝐞𝐝 𝐜𝐚𝐬𝐞𝐬. We've been fighting this cancer without understanding one of its key survival mechanisms. What interests me most is that 𝐂𝐗𝐂𝐋𝟖 𝐢𝐬𝐧'𝐭 𝐬𝐨𝐦𝐞 𝐦𝐲𝐬𝐭𝐞𝐫𝐢𝐨𝐮𝐬, 𝐮𝐧𝐝𝐫𝐮𝐠𝐠𝐚𝐛𝐥𝐞 𝐭𝐚𝐫𝐠𝐞𝐭. It's a well-studied protein with existing therapeutic approaches. This research opens doors to combination therapies that could dramatically improve radiation effectiveness. Sometimes the most important discoveries come from looking at what's been hiding in plain sight all along. #cervicalcancer #radiotherapy #cancerresearch #cxcl8 #innovation

New Winning Drugs in ER+ Breast Cancer? #medicine The treatment landscape for advanced estrogen receptor (ER)–positive, HER2-negative breast cancer is evolving with novel oral selective estrogen receptor degraders (SERDs). Two such agents, vepdegestrant and camizestrant, have been evaluated in clinical trials, offering insights into their potential to replace the standard intramuscular SERD, fulvestrant. Hot off the press #ASCO25! In the VERITAC-2 Phase 3 trial, published in NEJM yesterday, vepdegestrant was compared to fulvestrant in patients who had progressed on prior endocrine therapy and a CDK4/6 inhibitor. In the overall population, vepdegestrant did not significantly improve PFS (3.8 vs. 3.6 months; HR, 0.86; 95% CI, 0.70–1.06; P=0.16). However, in patients with ESR1 mutations, vepdegestrant extended median PFS to 5.0 months versus 2.0 months for fulvestrant (HR, 0.60; 95% CI, 0.43–0.83; P=0.002). Meanwhile, camizestrant has shown broader efficacy in the SERENA-6 trial published in NEJM today. This Phase 3 study involved patients on first-line aromatase inhibitor plus CDK4/6 inhibitor therapy. ESR1 mutations were tracked via ctDNA, and patients with these mutations were randomized to switch to camizestrant plus the same CDK4/6 inhibitor or continue standard therapy. Median PFS was 16.0 months for camizestrant versus 9.2 months for continued standard therapy, a 56% reduction in risk (HR, 0.44; 95% CI, 0.32–0.60; P<0.001). Camizestrant plus CDK4/6 inhibitors was well-tolerated with low discontinuation rates. Compared to fulvestrant, which is limited by its intramuscular administration and median PFS of 3.6 months, vepdegestrant (oral) offers targeted benefit in ESR1-mutant disease with PFS of 5.0 months. Camizestrant, also oral, demonstrated broader efficacy with a median PFS of 16.0 months in patients with ESR1 mutations detected through liquid biopsy while on first-line therapy. Both oral SERDs represent a major advance, offering convenient administration and potential to overcome resistance mechanisms. Vepdegestrant’s activity in ESR1-mutant disease highlights its targeted promise, while camizestrant’s robust efficacy and proactive treatment strategy may establish it as a new standard of care. These findings suggest a dynamic shift in the endocrine therapy landscape, with new options poised to replace fulvestrant and improve outcomes for patients with advanced ER-positive, HER2-negative breast cancer. Really very exciting for patients! References in comments. Follow Chris De Savi or ring the 🔔 icon to be notified of all his posts #healthcare #pharmaceuticals

🚀 The Future of Breast Cancer Treatment: How SERDs Are Changing the Game. The fight against hormone receptor-positive (HR+) breast cancer is entering a new era with Selective Estrogen Receptor Degraders (SERDs). Recent clinical breakthroughs and head-to-head data show why this class of drugs could soon become the new standard of care. Here’s what you need to know: 🔬 SERDs vs. SERMs: Why Mechanism Matters Traditional SERMs (like tamoxifen) block estrogen receptors but leave them intact, leading to resistance in many patients. SERDs (e.g., fulvestrant, elacestrant) take a more aggressive approach: ✔ They DESTROY estrogen receptors, making cancer cells more vulnerable. ✔ Work against ESR1 mutations (found in 25–40% of metastatic cases). ✔ New oral versions (like elacestrant) are replacing painful injections. 💡 Key Trial Data: In the EMERALD trial, elacestrant reduced progression risk by 45% in ESR1-mutant tumors. Giredestrant showed a 24% response rate in heavily pretreated patients (acSERA trial). Vepdegestrant demonstrated improvement in PFS among patients with an ESR1 mutation, reducing the risk of disease progression or death by 43% compared to fulvestrant. Camizestrant showed a 56% improvement in PFS in the Serena-6 study. 🚀 The Biggest Opportunities for SERDs 1️⃣ Overcoming Resistance 30–40% of HR+ tumors stop responding to current therapies. SERDs could fill this gap. Combination potential: Early data suggest SERDs + CDK4/6 inhibitors (e.g., palbociclib) could extend survival. 2️⃣ Moving Into Earlier Treatment Lines Trials like SERENA-6 are testing SERDs as first-line therapy, which could massively expand their use. 3️⃣ Next-Gen SERDs Are Coming PROTAC-based drugs (ARV-471) – Degrade ER even more effectively (Phase II data pending). Dual-action agents like AZ’s AZD9833 ⚠️ Challenges Ahead: ❌ Competition from CDK4/6 inhibitors (like Ibrance) in early-stage disease. ❌ Not all patients respond – Biomarkers (like ESR1 mutations) are still being refined. ❌ Generic fulvestrant is already here, putting pricing pressure on new entrants. 💡 The Bottom Line SERDs are no longer just a backup option—they’re becoming a central pillar of breast cancer treatment. With oral versions now approved and better biomarkers on the horizon, adoption is set to accelerate. 🔥 Hot Take: Within 5 years, SERDs could replace SERMs as the first-choice hormonal therapy for many patients. 👇 What’s your prediction? Will SERDs dominate, or will combination therapies take the lead? #BreastCancer #Oncology #SERD #PrecisionMedicine #CancerResearch #ClinicalTrials #market #biotech #investment Like | Comment | Repost to spread the word! 🚀

Has anybody else noticed this? Cell-specific targeting of cytokines is gaining some serious momentum, with prominent companies in the space - including Bright Peak Therapeutics and Asher Bio - garnering a lot of attention (and a lot of funding to advance their therapies into the clinic). Bright Peak just closed on $90M in Series C on June 30 and Asher just closed on $55M back in May. However, I've noticed something interesting... It seems to me that the ImmunoSTAT from Cue Biopharma is far superior to most other platforms in many highly relevant aspects, but the company doesn't seem to be getting as much attention...or funding.   Here's what I mean. I was able to uncover four aspects - though, I am sure there are some I have overlooked - that make the ImmunoSTAT a superior platform. 1. The ImmunoSTAT series offers higher degree of cell type-specificity - it is able to target highly specific T cell subsets based on their TCR. Most other platforms are simply directed by antibodies to common T cell targets like CD8, or PD-1. 2. While other platforms deliver a single cytokine per compound, CUE harbors 4 full-length IL-2 molecules per compound. This promotes a higher degree of immunogenic signaling per molecule-target interaction. 3. The ImmunoSTAT platform is not simply delivering a cytokine to a specific immune cell type, it is nucleating the formation of a full-blown immune synapse (TCR engagement AND IL-2 co-stimulation), eliciting a more comprehensive immunogenic signaling cascade and potentially more robust T cell stimulation. 4. ImmunoSTAT compounds are highly modular - the stimulatory cytokine and antigen peptide can be optimized depending on disease context, empowering the expansion of a diverse pipeline. --- My name is Jeff Martin. I am the Founder and Principal Consultant at Oncoleader, LLC. We provide biotech companies in the immuno-oncology space with a wide range of services to get your message to the right people. Check out my website - linked in comments and below my profile pic - for more details --- ***This post was in no way solicited by CUE and all of the opinions here are strictly my own.

Microbial trojan horses: disrupting the tumor microenvironment Solid #tumors are complex tissues gone wrong. Many different components comprises the tumor microenvironment. The extracellular #matrix (the fibrotic material provides the structural integrity to any #tissue) of tumor is heavily cross-linked than in normal tissues, making it very hard to penetrate, even for #immune cells. Solid tumor’s physical barriers and the way that it can biochemically affect the behavior of other cells makes them difficult to target with #immunotherapies. Non the less, #solidtumors are excellent sites for bacteria, as the tumor microenvironment is nutrient rich, heavily hypoxic, acidic and free from immune cells. However, in return, #bacteria offer the potential to be effective vessels for #therapeutic purposes due to their small size, mobility and their desire to live in tumors. Bacteria can be #engineered to produce and release an #enzymatic payload once they’re within a solid tumor, which breaks down some of the fibrotic components in the tumor’s extracellular matrix. By designing and constructing a #microscopic trojan horse that can naturally infiltrate tumor sites and break down the #extracellular matrix, the physical barrier that blocks #drug efficacy in solid tumors can be overcome. There are a number of therapeutics either commercially available or in advanced development stages that have curative potential, but don’t work in solid tumors because of these barriers to #infiltration. Bacteria can be designed with unique #genetic sequences that code for promoters that are active in the tumor. The tumor-induced activation of synthetic #biosensors then can trigger the production of an engineered #payload. Bacteria can express #enzymes that precisely modify specific components of the extracellular matrix, reducing its stiffness and increasing tumor irrigation. These payloads can be linked with secretion systems to ensure that they are released into the extracellular space of the tumor, targeting the extracellular matrix directly. Recent research shows that #synthetic biology platform can enable full responses in mouse models of breast cancer that previously did not respond to immunotherapies, by sensitizing them with bacterial products prior to drug delivery. Researcher found that remodeling the tumor with synthetic products enables full remission in response to immunotherapy. The animal experiment resulted in 100% survival. References: [1] https://lnkd.in/ecwAqDtF; [2] https://lnkd.in/eVNK6GwW [3] https://lnkd.in/ewAQY7V2; [4] https://lnkd.in/e238jZwm

🌐 Tumor-associated macrophages (TAMs) are a key immune component in the tumor microenvironment (TME) and are linked to poor prognosis in various cancers. 🔄 Besides their known role in promoting tumor growth and metastasis, recent studies highlight TAMs' involvement in immune suppression. 🎯 PD-L1 expression in host cells, including TAMs, is crucial for melanoma patients' response to PD-1 blockade immunotherapy. 🐭 Macrophage depletion in mice enhances the efficacy of PD-1/PD-L1 blockade, leading to increased recruitment and improved function of cytotoxic CD8+ T cells in tumors. ⚙️ Therapeutic strategies targeting macrophages show promising combinatorial effects with PD-1/PD-L1 blockade. 🔬 Researchers find that TAMs release PD-L1+ extracellular vesicles, with Akt promoting exosome secretion through MADD phosphorylation. 🚫 TAM-derived exosomes inhibit CD8 T cell proliferation and function. 🎯 Targeting macrophage RAB27A with LNPs sensitizes tumors to anti-PD-1 antibody. 🔍 Further investigations are essential: The study suggests that PD-L1 on TAM-derived exosomes plays a role in T cell suppression, but other molecules like TGF-β may also contribute. 📊 While LNPs were designed for preferential macrophage uptake, the study acknowledges the possibility of uptake by other cells, emphasizing the need for additional research. #translationalresearch #macrophages #exosomes #immunotherapy https://lnkd.in/eN4EXCG5

Scientists from the International Rice Research Institute (IRRI) have developed SpeedFlower, a robust, first-ever speed breeding protocol for rice that will achieve 4 to 5 crops of rice in one year, which is almost double of what has been possible in current breeding programs. SpeedFlower focuses on optimizing light spectrum, intensity, photoperiod, temperature, humidity, nutrient levels, and hormonal regulation to expedite growth, flowering, and maturity in rice. It has demonstrated flowering within just 60 days for tested rice varieties and achieved a 50% reduction in seed maturity time, irrespective of their natural flowering durations. The protocol is suitable for the vast majority of rice grown globally, including for indica and japonica.