Vadim Bichko

Why Gilead Sciences and Arcellx Anito-cel's data shows Promise in Multiple Myeloma Therapy Innovative Safety Profile: Early clinical data suggest anito-cel offers a reassuring safety advantage, with no reported cases of Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome—potentially addressing critical quality-of-life concerns. Encouraging Efficacy: With a 97% response rate and a median progression-free survival of 30.2 months in Phase 1, anito-cel demonstrates strong potential as an effective treatment option in heavily pretreated multiple myeloma patients. Cutting-Edge Technology: Anito-cel’s unique D-Domain binding technology may contribute to its promising safety and efficacy, reflecting innovation in CAR-T therapy design. #CellTherapy #MultipleMyeloma #InnovationInHealthcare #CAR_T #advancedtherapies #biotech #biotechnology #lifesciences #Data #ASH2024 https://lnkd.in/eCmJ_vP3

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In 2022 when Illumina and GRAIL leadership where touting how many lives would be saved if only the antitrust authorities got out of the way, here's what was really happening. Please read carefully, shows how this "life saving" test doesn't work: "[With the] San Francisco firefighters, the test did not identify the statistically expected number of cancers, provided false positives for half the cancers it did identify, and missed at least three cases of confirmed cancer. In other words, the exercise showed Galleri to be a disaster." "In this example prominently featured on GRAIL’s website and in marketing materials as an example of how “multi-cancer early detection screening can be critical for those at elevated cancer risk”—GRAIL provided 1,786 screenings to a group of San Francisco firefighters and their family members, a “high risk” group for certain kinds of cancer. During that testing round, which was conducted on December 6, 2022—Galleri generated six false positives and identified only five instances of cancer." "...such a result is alarming in light of the fact that, based on statistical experience, cancer should have been detected in about 29 (not five) of the 1,786 tests. Moreover, of the five instances of where cancer signals were identified, two individuals already knew they had cancer to begin with. Further, all of the instances of detected cancer were at a “late stage,” and where the cancer was too advanced to make a difference for the patients. One firefighter was diagnosed with stage 3 pancreatic cancer and is now in hospice, while another firefighter was diagnosed with lung cancer, which has now metastasized to the brain." "Galleri also missed at least six instances in which the San Francisco firefighters actually had cancer—failing to identify instances of melanoma, prostate cancer, and lymphoma that were identified by private doctors just months after the Galleri test indicated “no cancer signal.” "Further, in one instance in the San Francisco firefighters screening where Galleri generated a false positive, the patient underwent a painful bone marrow biopsy procedure to determine whether the patient did have cancer. In that case, the patient’s bone marrow biopsy procedure, clinically shown to involve “unbearable pain” to the “worst possible pain” a patient can experience, revealed that there was, in fact, no cancer." "The screenings provided to the San Francisco firefighters were an expensive “disappointment.” According to Tony Stefani, the organization’s founder, the screenings demonstrated that the probability of catching an early-stage cancer through the Galleri test was “negligible,” and the screenings only caught “some serious cancers at a later stage,” which likely would have been detected within one or two months without the test. Given the test’s high costs and useless real-world performance, Stefani stated that Galleri was a total “disappointment” and that the foundation had been sold a “bill of goods.” 🤯🤯🤯

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Engineered CD47 protects T cells for enhanced antitumour immunity Adoptively transferred T cells and agents designed to block the CD47–SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a ‘don’t eat me’ signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours. https://lnkd.in/eUsVmmw2

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Dyno Therapeutics is unlocking the future of #genetherapy with #AI-powered design. See how they’re solving the challenge of in vivo gene delivery by engineering better AAV capsids. With Benchling, they’ve scaled up their #ML by ✔️ Standardizing data across teams ✔️ Centralizing experimental data and metadata on an open platform ✔️ Increasing automation and instrument connectivity https://lnkd.in/dQJzhCDT #PoweredByAI #BuiltOnBenchling

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📍 The Single-cell Pediatric Cancer Atlas Hawkins et al. presented the Single-cell Pediatric Cancer Atlas (ScPCA) Portal, a data resource for uniformly processed single-cell and single-nuclei RNA sequencing data and de-identified metadata from pediatric tumor samples. Key points 📍 Over 500 samples from over 50 types of cancers 📍 Holding bulk RNA-seq, spatial transcriptomics, CITE-seq and cell hashing data 📍 Uniform data processing using scpca-nf workflow 📍 Available at https://lnkd.in/gRHsfKJ5 ➡ More details: https://lnkd.in/e-cPzt9Q #spatialomics #spatialbiology #singlecellanalysis #singlecell

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FDA issues new guidance on how to use circulating tumor DNA (ctDNA) as a biomarker in cancer treatment. MRD mentioned 29 times 🚀🚀🚀

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💡 Maximizing Performance in Microplate Shaking: Understanding the Limits of 3mm Incubator Shakers 💡 3mm orbit incubator shakers have been the biggest trend in shaking in the past 5 years with some papers claiming (multiple fold in some cases) increases in Viable Cell Densities (VCDs) and product titers when shaking 1ml of culture volume in 96DW blocks at 3mm/1000rpm versus 50mm/300rpm. When working with incubator shakers, especially those with a 3mm shaking orbit, it's essential to match the equipment to the task at hand. These shakers are great for specific applications but come with limitations that can affect experimental outcomes if not understood. 🔬 Optimal Use for 96-Deepwell Plates 3mm orbit shakers are well-suited for larger filling volume cultures in 96-deepwell plates. The small shaking orbit aligns with the dimensions and geometry of these plates, ensuring proper mixing, phase alignment, and oxygen transfer rates (OTR/kLa) of cultures op to 1ml. ❌ Why They Fall Short with 24-Deepwell Plates Due to the larger diameter of a well of a 24-deepwell plate, the speed of the liquid cannot keep up with shaker speed resulting in an out of phase condition. This can be seen in the video below and will lead to: - Inadequate mixing, leaving dead zones in the wells. - Poor oxygen transfer efficiency (low OTR/kLa values). - Splashing and formation of aerosols. - Suboptimal growth or reaction conditions, leading to inconsistent or poor results. ⚠️ The Lesson: Not all shakers are created equal for every plate type. Matching your equipment to your experimental setup is critical for reproducibility and success. If you're using 24-deepwell plates, use shakers with a larger orbit, better suited to these plate dimensions. 3mm shakers are trendy, 50mm shakers are forever! #LabTips #ShakingOrbit #OTR #DeepwellPlates #Biotechnology #CHO #HEK #CellCulture

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Glafabra Therapeutics (www.glafabra.com) is focusing on using cellular gene therapies (CGTs) to address enzyme deficiency disorders.  More than half of the enzymes involved in human metabolism (1546 genes - KEGG hsa011000) can cause a disease when they are absent.  Of these 909 genes seen in ClinVar database with at least one pathogenic variant #geneticdisease #drugdiscovery #cellulargenetherapies

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A new study by Rodriguez-Teja and colleagues reveals a critical link between aging, basement membrane stiffness, and prostate cancer development. As we age, collagen crosslinking due to advanced glycation end-products (AGEs) stiffens the basement membrane, impacting prostate epithelial cells. This stiffening activates Endo180, a receptor that triggers a metabolic shift towards oxidative phosphorylation (OXPHOS), promoting cancer hallmarks like increased proliferation and invasiveness. Utilizing Resipher for real-time oxygen consumption measurements, the study confirms that this metabolic change is directly tied to basement membrane stiffness. These findings not only underscore the role of Endo180 as a potential biomarker for early-stage prostate cancer but also open new avenues for therapeutic interventions. Read more here: https://lnkd.in/ejpu6jNk #ProstateCancer #BasementMembraneStiffness #Endo180 #OXPHOS #Aging #CancerMetabolism #CancerBiomarkers

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Check out this blog post regarding our STAR-CRISPR offering!

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🎤 uBriGene Presents Exclusive Sessions at SAPA 2024 @Philly CGT Annual Conference 🎤 🚀 We're thrilled to announce our participation at 2024 @Philly Cell and Gene Therapy Annual Conference with two exclusive sessions aimed at revolutionizing the field: 1️⃣ An Innovative Technology for High Yield and More Stable #CRISPR Guide RNA: Discover how our innovative approach of using in vitro transcription (IVT) in producing guide RNA (#gRNA) that can simplify the process while being more cost-effective and free of organic chemicals. Join us to delve into the future of precision gene editing. 2️⃣ How Could CDMO and Technology Innovations Make CGT Affordable: Dive into the intersection #CDMO of and technological advancements with uBriGene. Learn about our strategies to drive down costs without compromising quality or efficacy. Let's explore how cutting-edge technology can make #CellandGeneTherapy more accessible to all. 2024 @Philly Cell and Gene Therapy Annual Conference brings together the innovators and business leaders to foster collaborations and advance cell and gene therapy in the #GreaterPhiladelphia area. 💡 Join #uBriGene to be at the forefront of innovation and collaboration in the dynamic world of cell and gene therapy and let's make cutting-edge cell and gene technology more accessible!

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#LupusTherapeutics, the clinical affiliate of the Lupus Research Alliance Research Alliance, quickly connected with Dr. Brad Rovin at #ACR24 to explore the transformative role CAR T could play in advancing #lupus treatment and #lupusclinicalresearch. Watch the video to learn more.

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RAPT Therapeutics Therapeutics and Shanghai Jemincare Pharmaceutical Announce Exclusive License Agreement for Novel Long-Acting anti-IgE Antibody SOUTH SAN FRANCISCO, Calif., Dec. 23, 2024 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing novel therapies for patients with significant unmet needs in inflammatory diseases, and Shanghai Jemincare Pharmaceutical Co., Ltd (“Jemincare”), a subsidiary of Jiangxi Jemincare Group, a leading pharmaceutical company in China, today announced they have entered into an exclusive license agreement for JYB1904 (RAPT designation RPT904), a clinical-stage, half-life extended anti-immunoglobulin E (IgE) monoclonal antibody. Under the terms of the license agreement, RAPT is granted worldwide rights excluding mainland China, Hong Kong, Macau and Taiwan (together, the “Jemincare Territory”) to develop and commercialize RPT904. As consideration for the license, Jemincare receives a $35 million upfront license fee, up to $672.5 million in additional payments upon the achievement of various regulatory and commercial milestones, and royalties on future sales of RPT904 outside the Jemincare Territory. RPT904 is being developed to offer patients a potentially improved therapeutic option compared to omalizumab (marketed as Xolair®), an anti-IgE monoclonal antibody approved for several allergic disorders, including asthma, chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps and, most recently, food allergy. RAPT plans to pursue development of RPT904 initially in food allergy. Separately, Jemincare is conducting Phase 2 clinical trials of JYB1904 in China in asthma and CSU. “We’re delighted to partner with Jemincare and excited by RPT904 and its potential to be a novel best-in-class treatment option for patients with food allergy. Omalizumab’s rapid uptake in food allergy since its approval earlier this year confirms the high unmet need and large opportunity in this growing market,” commented Brian Wong M.D., Ph.D., President and CEO of RAPT. “RPT904 targets the same clinically validated epitope as omalizumab and combined with extended half-life, gives this molecule a best-in-class profile. We plan to initiate a Phase 2b clinical trial of RPT904 in food allergy in the second half of 2025.” https://lnkd.in/e92YkAmT

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Tissue-resident #NKcells do their own (G)landscaping | Jake Myers & friends "slaver over" Major New Study from Sonia Tugues Solsona & Co. with Breaking Insights* at Rockefeller University Press #JExpMed | #TGFβ | #IL15 | #ILC1 | In the latest issue of JEM, Colin Sparano, Darío Solís-Sayago et al** present compelling evidence that salivary gland trNK cells originate from cNK cells and are developmentally distinct from ILC1 cells. Mechanistically, they demonstrate that continuous autocrine TGF-β signaling drives salivary gland tissue residency and works in synergy with IL-15 to enhance Hobit-dependent cytotoxicity. *https://lnkd.in/eXYTdwjs **https://lnkd.in/e4iXZ4UJ Celentyx Ltd Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady FIGURE | Autocrine TGF-β signaling is required for the transition of conventional NK (cNK) cells to tissue-resident NK (trNK) cells in the salivary glands. IL-15 then synergizes with TGF-β to drive NK cells toward Hobit-dependent cytotoxicity | Courtesy of Jake Myers, Shanelle Reilly, PhD & Laurent Brossay |

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You don’t always want to enhance stability when genetic engineering… 🌿⚙️🧬 New research demonstrates that part of the symptomology of a plant disease (Witch’s Broom of jujube) is caused by a pathogen effector that OVER-stabilizes a native plant transcription factor. ⛓️‍💥 This pathogen effector locks down the dynamic, balancing feedback loops that are essential for healthy branch development and contributes to the diagnostic growth deformations of this disease! 🦠🥀 https://lnkd.in/es-TT9zt #bioengineering #syntheticbiology #molecularfarming (below, healthy branches of another tree, lime, with progressively impacted “brooms”)

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What does computation-driven drug discovery look like from a peptide's perspective? Hint: unnatural amino acids are necessary. A 2 nm view of Atommap.

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Conjunction Junction what's your Function? This video shows the migration and proliferation of two Bio-Blocks joining together: https://bit.ly/48UJE2c Lets collaborate, email us at [email protected]. #adiposestemcells, #cellculture, #tissueengineering, #mesenchymalstemcells

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There is great news for Illumina embedded in a new DeciBio liquid biopsy report. DeciBio projects the LB market to grow at 30% and reach $10B in 2029 and as they note, it's a crowded market with numerous approaches. But NGS is the common them as it's the ubiquitous technology for generating data for DNA, Methylation, RNA and multiomics (assuming genomics is base-line in omics). Trying to put a number on this effect from the figure below, NGS is the underlying technology for 151/217 = 70% of the LB companies. That makes LB a huge opportunity for Illumina (primarily) and other low cost SR providers. Situation is challenging for LR (PacBio and Oxford Nanopore Technologies) and slow/no scaling SR providers (Thermo Fisher Scientific, gotta buy Element Biosciences🤣).

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An Automated High-throughput Affinity Capture Mass Spectrometry Platform with Data Independent Acquisition A recent manuscript from researchers Hui Jing, Paul Richardson, Gregory Potts, Sameera Senaweera, Violeta Marin, Ryan McClure, Adam Banlasan, Hua Tang, James Kath, Renze (Arthur) Ma, and Jon Williams from AbbVie discusses the development, optimization, and application of a streamlined #chemoproteomics workflow Key Points: - #Automation of a workflow employing biotinylated probes and streptavidin magnetic beads for small molecule target enrichment has been developed to overcome the challenge of tedious and time-consuming sample preparation by leveraging the Integra Assist Plus from INTEGRA Biosciences. - A data-independent acquisition (#DIA) MS method was developed to establish a label-free quantitative chemical proteomic kinome profiling workflow leveraging the Evosep One platform from Evosep Biosystems and #Orbitrap Exploris 480 from Thermo Fisher Scientific. - Advancements in ultra-fast and sensitive MS instrumentation yields the possibility to perform miniaturized affinity capture and increase throughput to 100 SPD or faster. The full manuscript can be read here https://lnkd.in/gX2PhDMT To learn more about the Evosep One platform, visit our website www.evosep.com or reach out to me for more information.

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