Med - a Cell Press journal

Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy This review addresses key challenges in antibody-drug conjugate (ADC) development and corresponding optimization strategies from a structural perspective. It re-evaluates the relationship between target antigen expression and clinical response, the role of antibodies beyond targeting, and the effects of linker stability. Strategies enhancing ADC distribution, linker chemistry, and payload diversity are summarized.

Online Now: Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy

Microbial homeostasis and dysbiosis in physiological and pathological skin This review explores how the skin microbiota (bacteria, fungi, and viruses) sustains skin health physiologically and dysregulates in diseases like atopic dermatitis, wounds, and acne, highlighting microbial crosstalk and strain-specific impacts. It also previews emerging microbial therapies—such as phage use and engineered microbes—to restore skin microbial homeostasis.

Online Now: Microbial homeostasis and dysbiosis in physiological and pathological skin

A case of H10N3 avian influenza in a young woman Jing Wei et al. report on the effective and integrated clinical management routinely used for a female patient infected with the avian influenza A (H10N3) virus, which led to severe pneumonia, respiratory failure, and complications such as numbness and dysesthesia in her feet.

Online Now: A case of H10N3 avian influenza in a young woman

Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin Gao et al. have developed an optic fiber biosensor capable of detecting CLU protein in bile, which, integrated with digestive endoscopy, enables real-time in vivo diagnosis of cholangiocarcinoma. The technique has been thoroughly validated in pigs and patients, demonstrating exceptional diagnostic accuracy and rapid detection.

Online Now: Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin

Dengue virus infection reprograms baseline innate immune gene expression Ong et al. show that prior dengue, but not TAK-003 vaccination, results in reprogramming of innate immune gene expression. Reduced expression of antiviral genes in baseline seropositive individuals likely increased susceptibility to vaccine strain infection and augmented the antibody response to vaccination. Such increased susceptibility may also worsen future dengue.

Online Now: Dengue virus infection reprograms baseline innate immune gene expression

Efficacy of JAK inhibitor combined with protein A immunoadsorption in MDA5+ dermatomyositis with RPILD: A real-world study This study retrospectively evaluated the efficacy of antibody clearance therapy for MDA5+ DM patients in advanced stage. Results showed that protein A immunoadsorption plus JAK inhibitors-based treatment significantly increased 6-month lung transplantation-free survival in MDA5+ DM patients with RPILD, which was more prominent in patients with oxygen index lower than 200.

Online Now: Efficacy of JAK inhibitor combined with protein A immunoadsorption in MDA5+ dermatomyositis with RPILD: A real-world study

Machine learning-based identification of a transcriptomic blood signature discriminating between systemic autoimmunity and infection This study presents an innovative machine learning framework for distinguishing autoimmune diseases from infections with 98% accuracy using blood transcriptomic data. A new batch-correction approach and a 24-gene signature enabled high classification accuracy and hold promise for the development of targeted diagnostic assays in immunology and infectious disease research.

Online Now: Machine learning-based identification of a transcriptomic blood signature discriminating between systemic autoimmunity and infection

Anti-PD-1 antibody plus anlotinib vs. anlotinib alone in patients with refractory chondrosarcoma: A multicenter, non-randomized phase 2 FLAIL-C trial This trial provides the first evidence in a comparative setting for evaluating the activity of anti-PD-1 immunotherapy-based treatments in advanced chondrosarcoma. The combination of an anti-PD-1 antibody and anlotinib may be recommended as a systemic treatment option for dedifferentiated chondrosarcoma.

Online Now: Anti-PD-1 antibody plus anlotinib vs. anlotinib alone in patients with refractory chondrosarcoma: A multicenter, non-randomized phase 2 FLAIL-C trial

Trends and sociodemographic patterns in hypertension prevalence and treatment in China Cao et al. comprehensively estimated the trends in the hypertension prevalence, awareness, treatment, and control and the choice of antihypertensive drugs among Chinese adults. Hypertension prevalence in China has risen, while awareness, treatment, and control rates remain relatively low, highlighting the need for tailored policies to enhance hypertension prevention and management.

Online Now: Trends and sociodemographic patterns in hypertension prevalence and treatment in China

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Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II) In a phase 2 randomized clinical trial, Tang et al. demonstrate the efficacy and safety of adding sintilimab to SCRT-based TNT for patients with pMMR locally advanced rectal cancer. This therapeutic synergy of SCRT, sintilimab, and chemotherapy results in a superior complete response rate while maintaining a favorable safety profile.

Online Now: Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II)

Utility of circulating tumor DNA in management of diverse renal malignancies: Insights from a case series in adjuvant and recurrent/metastatic settings This case series describes six patients with diverse renal malignancies in whom ctDNA monitoring influenced clinical decision-making and treatment outcomes. The series highlights the potential of ctDNA as a complementary tool for detecting molecular residual disease, monitoring treatment response, and guiding therapy across a heterogeneous spectrum of renal malignancies.

Online Now: Utility of circulating tumor DNA in management of diverse renal malignancies: Insights from a case series in adjuvant and recurrent/metastatic settings

The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity GLP1 receptor agonists are reshaping obesity treatment with substantial weight loss outcomes, but concerns about cost, long-term adherence, and post-treatment support remain. This perspective explores the challenges of equitable access and sustainability to healthcare systems, arguing for strategic deployment alongside prevention of obesity to maximize public health impact.

Online Now: The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity

Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells Li et al. overcame ovarian cancer resistance and evasion to conventional CAR-T therapy by generating allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells. These CAR-NKT cells showed superior antitumor efficacy, a favorable safety profile, and resistance to allorejection, highlighting their unique advantages and off-the-shelf potential for treating ovarian cancer.

Online Now: Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

Current paradigm of EGFRins20 in non-small cell lung cancer: A long way forward EGFRins20 mutations in lung cancer are resistant to currently available traditional therapy, and while new drugs have been approved, more advancements are needed to improve patient outcomes. Novel therapeutics are currently under clinical investigation, and preliminary results are promising for future FDA approvals.

Online Now: Current paradigm of EGFRins20 in non-small cell lung cancer: A long way forward

Immune-related adverse events associated with cancer immunotherapy This review explores immune-related toxicities arising from the major immunotherapy classes. By comparing mechanisms, risk factors, and management strategies across therapeutic platforms, the authors provide critical insights for balancing efficacy and safety in evolving cancer immunotherapy landscapes.

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Recognizing overweight and obesity as chronic diseases and acknowledging root causes Obesity is a chronic disease regulated by genetic, environmental, and hormonal control of energy balance and is influenced by social and political factors. To de-stigmatize obesity, we need to recognize and treat the pathophysiology of overweight and obesity in the same way we recognize and treat other chronic diseases.

Online Now: Recognizing overweight and obesity as chronic diseases and acknowledging root causes

Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis Hegelmaier et al. describe the first use of anti-CD19 CAR T cells in refractory DAGLA antibody-associated encephalitis, achieving complete B cell depletion, anti-DAGLA antibody elimination in serum and CSF, and sustained clinical improvement. This case demonstrates CAR T cell therapy’s potential for severe autoimmune CNS disorders resistant to conventional treatments.

Online Now: Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis

Microbiota-derived metabolites: Key modulators of cancer immunotherapies Microbiota-derived metabolites shape immune responses and influence the efficacy and toxicity of cancer immunotherapies, including checkpoint inhibitors, CAR-T cells, and allogeneic stem cell transplantation. This review synthesizes mechanistic insights and clinical data, highlighting emerging biomarkers and therapeutic strategies to leverage personalized, metabolite-based treatment approaches in immuno-oncology.

Online Now: Microbiota-derived metabolites: Key modulators of cancer immunotherapies

Association of anti-PD-1 therapy with severe radiation-induced oral mucositis: A retrospective cohort study and validation in the CONTINUUM trial Zou et al. demonstrate that anti-PD-1 therapy raised the risk of severe radiation-induced oral mucositis (RIOM) in nasopharyngeal carcinoma patients under 45 years, receiving specific induction chemotherapy (docetaxel/cisplatin ± fluorouracil/capecitabine), or with a pre-radiotherapy neutrophil-lymphocyte ratio ≥2.5. Their nomogram facilitates optimized personalized monitoring and intervention strategies for severe RIOM during immunotherapy.

Online Now: Association of anti-PD-1 therapy with severe radiation-induced oral mucositis: A retrospective cohort study and validation in the CONTINUUM trial

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We’re delighted to welcome Future Science Prize 2024 winner Hongkui Deng @pku1898.bsky.social to the speaker lineup at the upcoming @CellSymposia #CSStemCells2025. Submit an abstract for a chance to join him in LA in November! http://dlvr.it/TLn6Xk

Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma Major trauma is a leading cause of death worldwide; however, translational targets have not been systematically identified. Pasqualini et al. identify a repertoire of trauma-homing ligand peptides targeting unique conformations of calcium-dependent receptors (as part of the trauma-related proteome, henceforth “traumome”), and advance one such ligand-receptor system toward translational applications.

Online Now: Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma

Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers This phase 1 translational study of plinabulin plus anti-PD-1 antibody after radiation therapy in immune checkpoint inhibitor-relapsed/refractory cancers showed good tolerability and encouraging disease control. Biomarker analyses differentiated responders from non-responders, suggesting that the baseline GEF-H1 immune gene signature might be of prognostic value for this plinabulin combination in future investigations.

Online Now: Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers

A phase 3, randomized trial to evaluate lot-to-lot consistency of V116, an adult-specific pneumococcal conjugate vaccine (STRIDE-4) Scott et al. conducted a randomized, global trial assessing the manufacturing consistency of three lots of V116 (an adult-specific, 21-valent pneumococcal conjugate vaccine); safety, tolerability, and immunogenicity were evaluated and compared with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Findings support the use of V116 for protecting adults against pneumococcal disease.

Online Now: A phase 3, randomized trial to evaluate lot-to-lot consistency of V116, an adult-specific pneumococcal conjugate vaccine (STRIDE-4)

Longitudinal progression of blood biomarkers reveals a key role of reactive astrocytosis in preclinical Alzheimer’s disease Varma et al. demonstrate that plasma concentrations of GFAP are increased a decade prior to cognitive impairment in AD and associated with pathology. Higher plasma GFAP levels are associated with greater GFAP immunoreactivity in mice. Reactive astrocytosis may be an early feature of AD and a promising drug target.

Online Now: Longitudinal progression of blood biomarkers reveals a key role of reactive astrocytosis in preclinical Alzheimer’s disease

Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial This randomized, double-blind trial evaluated the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder. Results showed greater reductions in depressive symptoms with higher LSD doses, supporting further investigation of LSD-assisted therapy in larger clinical trials for depression treatment.

Online Now: Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial

Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study Chen et al. investigated the efficacy of TTFields plus pembrolizumab and TMZ in newly diagnosed GBM. The triple regimen improved survival and enhanced anti-tumor immunity, especially in patients with bulky tumors. These findings suggest that TTFields can augment the efficacy of immune checkpoint inhibitors in GBM and potentially other tumors.

Online Now: Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study

Online Now: Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis

Online Now: Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission

Online Now: Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial