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Category: biotech/medical – Page 235

Tumor-Infiltrating Clonal Hematopoiesis and Pan-Cancer Prognosis in Patients With Solid Tumors

Tumor-infiltrating clonal hematopoiesis was detected in 18% of patients with solid tumors and associated with older age, prior cytotoxic chemotherapy, and reduced overall survival, especially in breast cancer.

This retrospective cohort study investigated the association of TI-CH with clinical factors and its impact on OS in patients with solid tumors. The prevalence of TI-CH in this patient cohort was higher than in treatment-naive cohorts but lower than that in cohorts with higher rates of cytotoxic chemotherapy and radiotherapy. In addition, the prevalence of TI-CH was higher in patients with MSI-high colorectal tumors than in those with MSS colorectal tumors. Analysis of clinical factors revealed that each decade of increasing age and a history of cytotoxic chemotherapy were significantly associated with higher odds of TI-CH. Although TI-CH was associated with worse OS in the whole cohort (pan-cancer analysis), this outcome was most pronounced in patients with breast tumors. Furthermore, TI-CH of GATA2 in the whole cohort and TI-CH of TET2 in patients with breast tumors had the most prominent associations with worse OS.

The accumulation of somatic variants in hematopoietic stem cells with age provides a competitive advantage, leading to CHIP.2 Additionally, cytotoxic chemotherapy induces gene-specific clonal expansion by allowing clones with variants in DNA damage response genes (eg, TP53, PPM1D) to outcompete other clones because such variants are associated with chemoresistance.25 The TI-CH prevalence in our study was intermediate between treatment-naive and treatment-experienced cohorts. It was higher than in the former due to prior therapy and lower than in the latter owing to reduced exposure to cytotoxic chemotherapy and radiotherapy. This finding is notable given this study cohort’s older age, a known factor for increasing CHIP prevalence.6, 7 Furthermore, we found that TI-CH prevalence was higher in patients with MSI-high colorectal tumors than in those with MSS colorectal tumors. To our knowledge, this finding has not been previously reported.

Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy is a major cause of hemorrhagic stroke, a frequent contributor to age-related cognitive impairment, and a key component in adverse responses to beta-amyloid (Aβ) immunotherapy. Defined by pathological deposition of Aβ in the small blood vessels of the brain, cerebral amyloid angiopathy is most often diagnosed on the basis of magnetic resonance imaging studies showing multiple hemorrhages or leptomeningeal blood products within or overlying the cerebral cortex. The disorder typically manifests as hemorrhagic stroke or as a contributing factor to cognitive decline and, less commonly, with transient focal neurologic symptoms or a cerebral inflammatory autoimmune syndrome.

Scientists Say This Simple Supplement May Actually Reverse Heart Disease

Scientists in Japan say a common supplement may actually help “unclog” certain diseased heart arteries from the inside out.

A simple food supplement sold in Japan may have helped reverse a dangerous form of heart disease that often resists standard treatment, according to researchers at Osaka University. The findings, originally published in the European Heart Journal, continue to attract attention because they describe something rarely seen in cardiology: clogged heart arteries becoming noticeably clearer after a nutritional intervention rather than conventional cholesterol lowering alone.

Scientists target a hidden form of heart disease.

Reprogramming myeloid crosstalk overcomes immune resistance in colorectal cancer

Immunotherapy resistance remains a significant clinical challenge in the treatment of colorectal cancer. A recent study by Mount Sinai researchers, published in Cell Reports Medicine, reveals that overcoming this resistance requires more than just activating cancer-fighting T cells; it depends on restoring crucial communication between T cells and myeloid cells, specifically macrophages. Using advanced preclinical models and single-cell analyses, the research team identified exhausted T cells and immunosuppressive macrophages as key drivers of treatment failure. To counter this, they tested a novel combination therapy that targets multiple immune checkpoint proteins (PD-1, CTLA-4, and LAG3) alongside TREM2, a marker found on suppressive macrophages. By successfully reprogramming the tumor microenvironment to simultaneously reinvigorate T cells and neutralize suppressive macrophages, this combination strategy achieved up to 100% tumor clearance in mismatch repair-deficient cancer models and over 70% clearance in typically resistant mismatch repair-proficient models. Furthermore, the approach established long-lasting immune memory against cancer recurrence, highlighting the profound clinical potential of rationally designed combination immunotherapies that address both T cell dysfunction and the suppressive tumor environment.

Mestrallet et al. show that T cell-myeloid interactions determine response to PD-1 blockade in colorectal cancer. Targeting TREM2 macrophages together with LAG3, CTLA4, and PD-1 reprograms the tumor microenvironment and drives antitumor immunity, achieving up to 100% tumor clearance in mismatch repair-deficient and 70% in mismatch repair-proficient models.

Nanoparticles overcome drug-resistant cancer via sequential drug release and photothermal therapy

Cancer cells frequently develop the ability to expel anticancer drugs before they can work—a phenomenon called multidrug resistance (MDR)—which is one of the leading reasons why chemotherapy fails in patients. Research published in the Journal of Controlled Release addresses that problem with a fundamentally new strategy: instead of simply increasing drug doses or switching drugs, researchers engineered nanoparticles that first disable the cancer cell’s drug-expulsion mechanism, and only then release the anticancer drug.

By combining this sequential drug delivery approach with photothermal therapy (using near-infrared laser light to heat and destroy the tumor), complete tumor elimination and 100% survival in a mouse model of drug-resistant cancer were achieved, with no detectable toxicity to normal tissues.

This remarkable drug delivery system was developed by an international research team led by Professor Eijiro Miyako at Tohoku University, who is also a Visiting Professor at Japan Advanced Institute of Science and Technology, in collaboration with the group of Drs. Alberto Bianco and Cécilia Ménard-Moyon at the French National Center for Scientific Research (CNRS)/University of Strasbourg.

Parkinson’s Patient Moves Freely Again After World-First Imp

Parkinson’s patient Thomas Matsson was the first in the world to receive 7 million lab-grown brain cells in 2023. Today, he can smell and play sports.

Researchers at Lund University in Sweden have successfully implanted 7 million lab-grown brain cells into a patient to treat Parkinson’s disease.

Swedish resident Thomas Matsson was the first in the world to test the method about a year ago.

Kanvas makes the microbiome druggable—and the implications are massive

Kanvas looks amazing! They’re systematically deciphering microbiomes and developing clinical-stage interventions to improve patient outcomes in oncology and beyond. Very impressive! I’m also especially interested in their approach to maternal envi­ron­mental enteric dysfunction (EED), which apparently affects 150M people!

Ever since the genomics revolution revealed how reliant the human organism is on its microscopic microbial cohabitants, the microbiome has been medicine’s most elusive frontier, promising better health if only we could untangle the trillions of interactions that influence nearly every facet of our physiology. But until now, effective medicines that harness the microbiome have been rare. Because of the diversity of microbial species and the complexity of host-to-microbe interactions, as well as the lack of a reliable, easily manufactured drug modality (the package that delivers a medicine’s therapeutic effect), the microbiome has been hard to treat, despite its importance to functions like immune response. Microbiome science has disappointed patients, doctors, founders, and investors.

That’s why DCVC is so excited about the cascade of recent developments at Kanvas Biosciences, which is moving the field beyond descriptive profiling of the microbiome to translating comprehensive biochemical insights into clinically useful products. In the past few weeks, the Princeton-based spatial biology company has kicked off a Phase 1 clinical trial for its first drug candidate, secured significant new backing from the Gates Foundation (closing a $48 million Series A financing, bringing Kanvas’s total funding to $78 million), and bolstered its scientific leadership by adding one of the most respected names in bioengineering to its board.

Clinical milestone

The most significant milestone in Kanvas’s evolution is the dosing of the first patients in a Phase I clinical trial for KAN-4. This live biotherapeutic product (LBP), resembling an ordinary pill, treats the colitis that many cancer patients develop after receiving immune checkpoint inhibitors (ICIs), allowing them to remain on the life-saving therapy longer.