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Antibody-drug conjugates as game changers in bladder cancer: current progress and future directions

In recent years, ADCs have emerged as a transformative therapeutic modality in oncology, offering a promising avenue for the treatment of bladder cancer. ADCs combine the specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic agents, enabling targeted delivery of payloads to tumor cells while sparing healthy tissues. This unique mechanism of action has led to significant advancements in the treatment landscape, particularly for cancers that are resistant to conventional therapies (5). In bladder cancer, ADCs have demonstrated remarkable efficacy by targeting specific tumor-associated antigens, such as nectin-4 and HER2, thereby inducing tumor cell apoptosis and inhibiting metastasis. For example, Enfortumab vedotin (targeting NECTIN-4) achieved a median overall survival of 12.9 months in the EV-301 trial (vs. 9.0 months with chemotherapy) (6). Similarly, trastuzumab deruxtecan, a HER2-directed ADC, has demonstrated promising antitumor activity in HER2-expressing bladder cancer (7), offering a potential therapeutic option for this subset of patients.

Despite these promising developments, several challenges persist in the clinical application of ADCs for bladder cancer. Key issues include the durability of therapeutic responses, the management of off-target toxicities, and the heterogeneity of antigen expression across different patient subtypes (8). Moreover, the optimal integration of ADCs with existing treatment paradigms, such as immune checkpoint inhibitors and chemotherapy, remains an area of active investigation (9). Addressing these challenges is crucial for maximizing the therapeutic potential of ADCs and improving patient outcomes.

This study provides a comprehensive evaluation of the current landscape of ADC-based therapies for bladder cancer, with a focus on their mechanisms of action, clinical efficacy, and safety profiles. We systematically review ongoing clinical trials, highlighting the most promising ADC candidates and their respective targets. Furthermore, we explore emerging strategies to enhance the precision and durability of ADC therapies, including the development of novel linkers, payloads, and antibody engineering techniques. By synthesizing the latest clinical data, this review aims to offer valuable insights into the future directions of ADC research and their potential to revolutionize bladder cancer treatment. Our findings underscore the importance of continued innovation in ADC technology and the need for personalized approaches to overcome the limitations of current therapies, ultimately paving the way for more effective and safer treatment options for patients with bladder cancer.

Why biology could be the future of computing and engineering

Australian researchers are turning to nature for the next computing revolution, harnessing living cells and biological systems as potential replacements for traditional silicon chips. A new paper from Macquarie University scientists outlines how engineered biological systems could solve limitations in traditional computing, as international competition accelerates the development of “semisynbio” technologies.

Living computers, organs-on-a-chip, data storage in DNA and biosecurity networks that detect threats before they spread—these aren’t science fiction concepts but emerging realities. A team from Macquarie University and the ARC Center of Excellence in Synthetic Biology (COESB) has explored this convergence of biological and digital technologies in a Perspective paper published in Nature Communications.

The Macquarie University authors—Professor Isak Pretorius, Professor Ian Paulsen and Dr. Thom Dixon (who are also affiliated with the ARC Center of Excellence in Synthetic Biology), Professor Daniel Johnson and Professor Michael Boers—draw on decades of combined experience to explain why harnessing bio-innovation can proactively shape the future of computing .

Graphene foam supports lab-grown cartilage for future osteoarthritis treatments

Boise State University researchers have developed a new technique and platform to communicate with cells and help drive them toward cartilage formation. Their work leverages a 3D biocompatible form of carbon known as graphene foam and is featured on the cover of Applied Materials and Interfaces.

In this work, the researchers aim to develop new techniques and materials that can hopefully lead to new treatments for osteoarthritis through . Osteoarthritis is driven by the irreversible degradation of hyaline cartilage in the joints, which eventually leads to pain and disability, with complete joint replacement being the standard clinical treatment. Using custom-designed and 3D-printed bioreactors with electrical feedthroughs, they were able to deliver brief daily electrical impulses to cells being cultured on 3D graphene foam.

The researchers discovered that applying direct to ATDC5 cells adhered to the 3D graphene foam bioscaffolds significantly strengthens their and improves —key metrics for achieving lab-grown cartilage. ATDC5 cells are a murine chondrogenic progenitor cell line well studied as a model for cartilage tissue engineering.

ENGINEERING EARTH: Sci-Fi Solutions to Earth’s Problems — 4K Full Documentary

High quality 4K Download: https://melodysheep.gumroad.com/l/udffp // Soundtrack: https://melodysheep.bandcamp.com/album/engineering-earth-original-soundtrack // Mankind has become the pilot of spaceship earth, whether we like it or not. Half of all habitable land on earth is now dedicated to supporting human activity. And as of the year 2020, the mass of all man-made materials now outweighs the mass of all life forms on earth.

Despite all this, we are still newcomers – untrained pilots steering an ancient, ever-changing planet. If we want to survive long-term and continue to grow, we will have to make bigger technological leaps than ever before.

This film explores the wildest, most ambitious, most dangerous ideas to keep Earth and humanity thriving, by protecting each of its layers – from the lithosphere to the stratosphere.

Many of our ideas may never materialize, but by dreaming them up, we can open our minds to the full potential of human willpower and intellect. The future is ours to build.

Thanks for watching everybody.

Music, Visuals, Sound & Story by Melodysheep (John D. Boswell)
melodysheep.com.
instagram: @melodysheep_
twitter: @musicalscience.

Narrated by Will Crowley.

Could This Biocomputer Revolutionize Neuroscience and Drug Discovery? Dive into the World of Human Brain Cells on a Chip!

Australian startup Cortical Labs unveils CL1, a groundbreaking biocomputer using human neurons on silicon chips. This fusion offers real-time learning and adaptation, revolutionizing neuroscience and biotech research. Could this be the dawn of bioengineered intelligence?

CRISPR gene editing in blood stem cells linked to premature aging effects: Study offers solutions

Scientists at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, have found that gene editing using CRISPR-Cas9 in combination with AAV6 vectors can trigger inflammatory and senescence-like responses in blood stem cells, compromising their long-term ability to regenerate the blood system.

The study, published in Cell Reports Medicine, outlines new strategies to overcome this hurdle, improving both the safety and efficacy of -based therapies for inherited blood disorders.

The research was led by Dr. Raffaella Di Micco, group leader at SR-Tiget, New York Stem Cell Foundation Robertson Investigator and Associate Professor at the School for Advanced Studies (IUSS) of Pavia, in collaboration with Professor Luigi Naldini, Director of SR-Tiget, and several European research partners.

AI used to design immune-safe ‘zinc finger’ proteins for gene therapy

Machine learning models have seeped into the fabric of our lives, from curating playlists to explaining hard concepts in a few seconds. Beyond convenience, state-of-the-art algorithms are finding their way into modern-day medicine as a powerful potential tool. In one such advance, published in Cell Systems, Stanford researchers are using machine learning to improve the efficacy and safety of targeted cell and gene therapies by potentially using our own proteins.

Most human diseases occur due to the malfunctioning of proteins in our bodies, either systematically or locally. Naturally, introducing a new therapeutic protein to cure the one that is malfunctioning would be ideal.

Although nearly all therapeutic protein antibodies are either fully human or engineered to look human, a similar approach has yet to make its way to other therapeutic proteins, especially those that operate in cells, such as those involved in CAR-T and CRISPR-based therapies. The latter still runs the risk of triggering immune responses. To solve this problem, researchers at the Gao Lab have now turned to machine learning models.

Promising breakthroughs in amyotrophic lateral sclerosis treatment through nanotechnology’s unexplored frontier

This review explores the transformative potential of nanotechnology in the treatment and diagnosis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder characterized by motor neuron degeneration, muscle weakness, and eventual paralysis. Nanotechnology offers innovative solutions across various domains, including targeted drug delivery, neuroprotection, gene therapy and editing, biomarker detection, advanced imaging techniques, and tissue engineering. By enhancing the precision and efficacy of therapeutic interventions, nanotechnology facilitates key advancements such as crossing the blood-brain barrier, targeting specific cell types, achieving sustained therapeutic release, and enabling combination therapies tailored to the complex pathophysiology of ALS.