bims-carter 2025-08-17 papers

bims-carter

Biomed News

on CAR-T Therapies

Issue of 2025–08–17
eighteen papers selected by
Luca Bolliger, lxBio

Genetically engineered T cell and tumour-infiltrating lymphocyte therapies.
A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy.
Harnessing the chimeric antigen receptor engineered cells in gastrointestinal cancer immunotherapy.
Neurotoxicity associated with chimeric antigen receptor T-cell therapy.
Transfection Technologies for Next-Generation Therapies.
Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies.
Commercialization of cell and gene therapy in Canada: Current landscape, challenges and opportunities.
Pooled CAR-T screening in nonhuman primates identifies designs with enhanced proliferation, trafficking, and persistence.
Exploiting TCR Repertoire Analysis to Select Therapeutic TCRs for Cancer Immunotherapy.
Advancements in antibody-drug conjugates as cancer therapeutics.
Major Adverse Events with Chimeric Antigen Receptor T-Cell Therapy: Presentation, Diagnosis, and Resuscitation.
"Snip, snip, cure"? Philosophical, legal and biomedical perspectives on novel somatic genomic therapies.
Chats and Spats of Autophagy and Innate Immune Systems.
Combining antibody-drug conjugates with immune checkpoint inhibitors: A new paradigm for breast cancer therapy.
A roadmap for personalized medicine: the findings of the IC2PerMed project.
Process mining in healthcare: a tertiary study.
A Bibliometric Analysis on Research Trends in Paediatric Epilepsy Treatment From 2005 to 2025.
Using spatial statistics to infer game-theoretic interactions in an agent-based model of cancer cells.

Swiss Med Wkly. 2025 Jul 24. 155 4279

Genetically engineered T cell and tumour-infiltrating lymphocyte therapies.

Heinz Läubli, Andreas Holbro.

Haemato-oncology has made significant progress in recent years, particularly through the development of innovative immunotherapeutic approaches such as CAR T cell (chimeric antigen receptor T cell) and tumour-infiltrating lymphocyte therapies. Both methods use the patient's own immune system to treat cancer, but in different ways. CAR T cell therapy is a form of immunotherapy in which the patient's own T cells are genetically modified. CAR T cell therapies have proven to be particularly effective in haematological B-cell neoplasms, such as B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell lymphomas, as well as in multiple myeloma. Tumour-infiltrating lymphocyte therapy, on the other hand, exploits the natural ability of T cells to recognise tumour-associated antigens of tumour cells with the T cell receptor. Tumour tissue is taken from the patient then tumour-infiltrating lymphocytes are isolated from it. These tumour-infiltrating lymphocytes are expanded ex vivo to increase their number and activity. This review discusses the principles of these innovative therapies. Both therapies represent significant advances in personalised cancer treatment and offer new hope for our cancer patients.

DOI: https://doi.org/10.57187/s.4279
Front Syst Biol. 2024 ;4 1380018

A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy.

Sarah Minucci, Scott Gruver, Kalyanasundaram Subramanian, Marissa Renardy.

  Chimeric antigen receptor T (CAR T) cell therapy has shown remarkable success in treating various leukemias and lymphomas. Cellular kinetic (CK) and pharmacodynamic (PD) behavior of CAR T cell therapy is distinct from other therapies due to its living nature. CAR T CK is typically characterized by an exponential expansion driven by target binding, fast initial decline (contraction), and slow long-term decline (persistence). Due to the dependence of CK on target binding, CK and PD of CAR T therapies are inherently and bidirectionally linked. In this work, we develop a semi-mechanistic model of CAR T CK/PD, incorporating molecular-scale binding, T cell dynamics with multiple phenotypes, and tumor growth and killing. We calibrate this model to published CK and PD data for a CD19-targeting CAR T cell therapy. Using sensitivity analysis, we explore variability in response due to patient- and drug-specific properties. We further explore the impact of tumor characteristics on CAR T-cell expansion and efficacy through individual- and population-level parameter scans.

Keywords:  CAR T-cell therapy; cellular kinetics; mechanistic modeling; quantitative systems pharmacology; sensitivity analysis

DOI:  https://doi.org/10.3389/fsysb.2024.1380018
Int Immunopharmacol. 2025 Aug 09. pii: S1567-5769(25)01312-8. [Epub ahead of print]164 115321

Harnessing the chimeric antigen receptor engineered cells in gastrointestinal cancer immunotherapy.

Arash Dadvand, Mohsen Nooroulahi, Somaieh Matin, Elnaz Faghfuri.

  Gastrointestinal (GI) cancers pose a significant global health concern. Their prevalence is continually increasing, and managing them remains a significant clinical hurdle. Adoptive cell therapies designed to express chimeric antigen receptors (CARs) or transgenic T cell receptors (TCRs) to identify and destroy cancer cells have emerged as a promising strategy for achieving long-term remissions in cancer patients. To be effective, the engineered cells must persist at therapeutically sufficient levels while minimizing off-tumor toxicities, which has proven difficult to realize outside of hematologic malignancies. This review comprehensively discusses the progress and use of CAR-immune cells in treating GI cancers. We looked into different sources of these cells, CAR design strategies, and the latest advancements in CAR-cell therapy for GI cancers, while providing organ-specific preclinical and clinical insights across colorectal, gastric, hepatic, and pancreatic malignancies. Moreover, we discussed the current challenges and suggested potential methods to improve the efficacy and safety of CAR-cell therapy. This review emphasizes the unique potential of CAR-NK cells as low-toxicity, "off-the-shelf" alternatives to CAR-T cells. It details innovative strategies to overcome solid tumor challenges-including metabolic reprogramming, dual-targeting approaches, and microenvironment modulation. It is concluded that CAR cells have significant potential to revolutionize the treatment of gastrointestinal cancer, paving the way for rational combinations that open up new therapeutic perspectives.

Keywords:  CAR-NK cell therapy; CAR-T cell therapy; Chimeric antigen receptor (CAR); Gastrointestinal cancer; Immunotherapy

DOI:  https://doi.org/10.1016/j.intimp.2025.115321
J Neuroimmunol. 2025 Aug 09. pii: S0165-5728(25)00198-5. [Epub ahead of print]407 578717

Neurotoxicity associated with chimeric antigen receptor T-cell therapy.

Miriam Wronski, Robb Wesselingh, Christina Kazzi, Nabil Seery, Katherine Ko, Jian Li, Tracie H Tan, Ty Simpson, Cassandra Abbott, Shaun Fleming, Shafqat Inam, Constantine S Tam, Shu Min Wong, Terence O'Brien, Anneke van der Walt, Andrew Spencer, Helmut Butzkueven, Mastura Monif.

  Chimeric antigen receptor T cell (CAR-T) therapy involves reengineering patient-derived or donor-derived T cells to express a synthetic CAR that can recognise specific cell-surface antigens, independently of major histocompatibility complex molecules. As of March 2025, six autologous CAR-T cell products have received regulatory approval from the United States Food and Drug Administration (FDA) for B-cell derived haematological malignancies and multiple myeloma, delivering effective and durable treatment responses. All currently approved CAR-T cell therapy products target either CD19 or B-cell maturation antigen (BCMA). However, there is an expansive list of new CAR-T constructs and/or indications currently being explored in the pre-clinical stages and clinical trials. Although the therapeutic potential of CAR-T cell therapy is substantial, the more widespread application of CAR-T cell therapy faces challenges, including overcoming unique and clinically significant CAR-T therapy-associated toxicities, namely cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS). CAR-T cell-associated neurotoxicity can present with a diverse range of neurological and cognitive symptoms and signs, including tremor, dysgraphia, cognitive dysfunction, aphasia, seizures, and rarely cerebral oedema and death. As new CAR-T constructs and indications enter the therapeutic landscape, new class-specific toxicities have also emerged, including delayed-onset neurotoxicity with features of parkinsonism, as seen with BCMA-directed therapies in the pivotal clinical trials for multiple myeloma. Whilst much progress has been made in understanding CRS, comprehensive information about the clinical, biological and radiological correlates of CAR-T cell-associated neurotoxicity, and its mechanistic underpinnings remain largely unknown. Furthermore, prophylactic or pre-emptive intervention strategies have been hindered by the lack of predictive or diagnostic biomarkers for ICANS. Considering the lack of targeted therapies for ICANS, detailed analysis of the associated biomarkers remains a key area of unmet need in the field. This review provides a detailed analysis of CAR-T cell-associated neurotoxicity, with a focus on the novel pathophysiological insights into disease mechanisms, the clinical manifestations and diagnostic evaluation, candidate biomarkers for neurotoxicity, and the current therapeutic landscape for ICANS management.

Keywords:  CAR; CAR-T cell therapy; ICANS; chimeric antigen receptor T cell therapy; chimeric antigen receptor therapy; immune effector cell-associated neurotoxicity syndrome

DOI:  https://doi.org/10.1016/j.jneuroim.2025.578717
J Clin Med. 2025 Aug 05. pii: 5515. [Epub ahead of print]14(15):

Transfection Technologies for Next-Generation Therapies.

Dinesh Simkhada, Su Hui Catherine Teo, Nandu Deorkar, Mohan C Vemuri.

  Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute's online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability.

Keywords:  CAR-T cell therapy; antisense oligonucleotides (ASOs); gene delivery; gene editing; gene therapy; lipid nanoparticles (LNPs); mRNA therapeutics; non-viral vectors; regenerative medicine; siRNA; transfection

DOI:  https://doi.org/10.3390/jcm14155515
Hemasphere. 2025 Aug;9(8): e70182

Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies.

Charles Agbuduwe, John Maher, John Anderson.

Gamma delta (γδ) T cells, which constitute about 5%-10% of peripheral blood lymphocytes, play key roles in tumor immunosurveillance and are often enriched within epithelial tissues. They are unique in their Major Histocompatibility Complex-independent antigen recognition via the γδ T-cell receptor (TCR) as well as via innate receptors, making them ideal1 candidates for allogeneic "off-the-shelf" cell therapy products. In humans, two main structural subsets of γδ T cells-Vδ1 and Vδ2-have been defined, which differ in TCRδ chains, effector function, and tissue localizations. Vδ2 T cells constitute the majority of γδ T cells in peripheral blood and can be expanded with aminobisphosphonates such as zoledronic acid. In recent years, the potent antitumor functions of Vδ1 T cells have also been recognized, and new expansion protocols are being developed. Given the ample preclinical evidence of γδ T-cell efficacy against hematological malignancies, several γδ T-cell-based cell therapy products are currently in clinical development, and there has been an exponential increase in the number of adoptive γδ T-cell therapy clinical trials. This comprehensive review provides an overview of the rationale for γδ T-cell therapy, ongoing clinical trials, as well as the challenges and future role of γδ T-cell-based immune therapies in hematology.

DOI: https://doi.org/10.1002/hem3.70182
Drug Discov Today. 2025 Aug 13. pii: S1359-6446(25)00166-7. [Epub ahead of print] 104453

Commercialization of cell and gene therapy in Canada: Current landscape, challenges and opportunities.

Logan S Germain, Louise M Winn.

  Cell and gene therapies (CGTs) offer transformative treatments for certain genetic diseases and cancers, with a growing number of global approvals. Yet Canadian commercialization lags behind the USA and Europe. This review identifies key barriers and proposes policy solutions informed by international examples. A policy-oriented environmental scan was conducted using regulatory documents, peer-reviewed literature, government reports, and industry publications. Barriers and solutions are organized into four domains: regulation, manufacturing, pricing and reimbursement, and access and equity. Despite recent investment downturns in this therapeutic area, Canada's approval of its first clustered regularly interspaced short palindromic repeats (CRISPR)-based therapy and chimeric antigen receptor (CAR) T-cell expansion suggest future growth. Strategic reforms could improve domestic CGT innovation, affordability, and equitable access.

Keywords:  cell and gene therapy (CGT); commercialization; environmental scan; health technology assessment; market access; regulatory policy

DOI:  https://doi.org/10.1016/j.drudis.2025.104453
Blood. 2025 Aug 14. pii: blood.2025028683. [Epub ahead of print]

Pooled CAR-T screening in nonhuman primates identifies designs with enhanced proliferation, trafficking, and persistence.

Lucy H Maynard, Eric J Cavanaugh, Haiying Zhu, Carly E Starke, Sarah M Doherty, Teresa K Einhaus, Ailyn C Pérez-Osorio, Laurence Stensland, Cameron Blair, Aoife M Roche, John K Everett, Robert D Murnane, Michelle E Hoffman, Veronica Nelson, Sarah Althea Herrin, Chad Littlewood, Kaycee Camou, Erica Wilson, Christopher Wessel, Frederic Bushman, Keith R Jerome, Hans-Peter Kiem, Christopher William Peterson.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized treatment for B-cell malignancies, yet over 60% of patients relapse within one year, often due to insufficient CAR-T persistence. While mouse and primary cell models have been instrumental in advancing CAR-T therapy, they frequently fail to predict clinical outcomes, underscoring the need for more translationally relevant models. To address this limitation, we conducted the first systematic evaluation of CAR structure-function relationships in an immunocompetent nonhuman primate (NHP) model. We engineered an array of 20 CD20-targeted CARs with distinct combinations of hinge, transmembrane, and costimulatory domains. Following ex vivo characterization, we administered pooled autologous CAR-T arrays to three NHPs and tracked CAR abundance longitudinally using a novel digital droplet PCR assay. Ex vivo, CAR-T cells incorporating the MyD88-CD40 costimulatory domain exhibited markedly distinct functional profiles, including increased activation, unique cytokine secretion, tonic signaling, and resistance to exhaustion. In vivo, MyD88-CD40 CARs expanded dramatically, comprising up to 100% of peripheral CAR-T cells and significantly outperforming canonical CD28- and 4-1BB-based CARs. This expansion was associated with robust B-cell depletion across all animals. MyD88-CD40 CARs, particularly those with a CD28 hinge and transmembrane domain, demonstrated superior trafficking to secondary lymphoid tissues and persistence through study endpoint, unlike other CARs which waned by day 28. Our findings highlight the value of NHP models for screening CAR designs and identify MyD88-CD40 CARs as candidates with unmatched potency. The unique functional attributes conferred by this domain may provide key insights into features that drive enhanced CAR-T cell activity.

DOI: https://doi.org/10.1182/blood.2025028683
Cells. 2025 Aug 07. pii: 1223. [Epub ahead of print]14(15):

Exploiting TCR Repertoire Analysis to Select Therapeutic TCRs for Cancer Immunotherapy.

Ursule M Demaël, Thunchanok Rirkkrai, Fatma Zehra Okus, Andreas Tiffeau-Mayer, Hans J Stauss.

  Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown.

Keywords:  T cell receptor; TCR repertoire; TCR sequencing; TCR-T cells; cancer immunotherapy; cell therapy; clonality; meta-clonotype; tumour infiltrating lymphocytes

DOI:  https://doi.org/10.3390/cells14151223
J Natl Cancer Cent. 2025 Aug;5(4): 362-378

Advancements in antibody-drug conjugates as cancer therapeutics.

Jung Yin Fong, Zhixin Phuna, Di Yang Chong, Christophorus Manuel Heryanto, Yu Shyan Low, Khang Chiang Oh, Yan Huen Lee, Allan Wee Ren Ng, Lionel Lian Aun In, Michelle Yee Mun Teo.

  Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, highlighting approved ADCs and promising candidates in clinical trials, while also addressing key challenges such as stability, half-life, and systemic toxicity. This review is based on an extensive literature survey from major databases such as Scopus and Web of Science, with a focus on keywords like "antibody-drug conjugates", "ADC advancements", and "next-generation ADC technologies". By integrating insights from both preclinical and clinical perspectives, we highlight the transformative potential of ADCs in advancing modern cancer therapy.

Keywords:  Antibody; Antibody-drug conjugates; Cancer; Linker; Targeted therapy

DOI:  https://doi.org/10.1016/j.jncc.2025.01.007
Ann Emerg Med. 2025 Aug 16. pii: S0196-0644(25)01049-2. [Epub ahead of print]

Major Adverse Events with Chimeric Antigen Receptor T-Cell Therapy: Presentation, Diagnosis, and Resuscitation.

Kiril Dimitrov, Florian Merkle, Marketa Dimitrov, Svatava Merkle, Alex Hoover, Veronika Bachanova.

  With continued advances in targeted cancer treatment, such as chimeric antigen receptor T-cell (CAR-T) therapy, emergency departments (EDs) across the United States should be prepared to diagnose and care for patients who experience unique adverse events related to CAR-T administration. CAR-T therapy is the first genetically modified cellular therapy approved by the Food and Drug Administration for treatment of several hematologic malignancies, including leukemia, lymphoma, and myeloma. The side effect profile differs from conventional chemotherapy and consists of a spectrum of immune-mediated clinical manifestations, particularly cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and the more recently described immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome can present with nonspecific symptoms and signs and should be differentiated from other life-threatening pathologies such as sepsis and meningitis. There is limited guidance for emergency physicians and staff regarding the recognition and management of CAR-T complications, both in adult and pediatric patient care settings. This clinical review provides insight into the common and less common CAR-T toxicities, including symptomatology, diagnostic approach, and fundamental principles of complication management in adult and pediatric patients undergoing CAR-T therapy.

Keywords:  CAR-T toxicity management; Chimeric antigen receptor T-cell therapy; Cytokine release syndrome; Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome; Immune effector cell-associated neurotoxicity syndrome

DOI:  https://doi.org/10.1016/j.annemergmed.2025.07.005
Med Health Care Philos. 2025 Aug 11.

"Snip, snip, cure"? Philosophical, legal and biomedical perspectives on novel somatic genomic therapies.

Johanna Risse, Lothar Pietrek, Tobias Cantz, Merlin Krzemien, Jan Schnalke, Reto Eggenschwiler, Thomas Heinemann, Hans-Georg Dederer.

  The advent of innovative techniques, such as the CRISPR/Cas system, has opened up a new range of possibilities for modifying the genome, with the potential to address previously unmet therapeutic needs of patients with genetic diseases. These new possibilities have not only raised ethical concerns but also challenged existing classifications of genome modification techniques. While the legal status of some of these new therapies remains uncertain, there is an ongoing debate within philosophy of biology about the information-related metaphors adopted by scientists to describe and classify the genome and its therapeutic modification. Given the continuing advance of new genomic therapies, we show, employing an interdisciplinary approach, that a comprehensive framework for the classification of these technologies is needed to resolve legal and philosophical issues. The first section provides an analysis of the current state of novel genome-modifying techniques in medical genetics. In the second section, we assess the regulatory status of these techniques within the European regulatory framework for advanced therapy medicinal products (ATMPs). Drawing on these results, we argue in the third section from a philosophical perspective that metaphors, such as 'editing' the genome, which are based on a conception of the genome as linear information, cannot adequately capture the breadth of advanced genomic technologies. To accurately categorise these techniques in a manner that meets their diverse applications, we propose introducing the umbrella term 'somatic genomic therapies' (SGTs). Urging an integrative approach to defining and classifying new technologies in medical genetics, we advocate for the development of an integrative concept of SGTs.

Keywords:  Advanced therapy medicinal products; CRISPR/Cas; Gene therapy; Genome editing; Postgenomic era

DOI:  https://doi.org/10.1007/s11019-025-10284-5
J Mol Biol. 2025 Aug 11. pii: S0022-2836(25)00453-X. [Epub ahead of print] 169387

Chats and Spats of Autophagy and Innate Immune Systems.

Soumya Kundu, Swati Chauhan, Kollori Dhar, Sriram Varahan, Santosh Chauhan.

The innate immune system and autophagy are the two fundamental pillars of host defense. Both processes coordinate to maintain cellular homeostasis and protect from multiple threats, ranging from invading pathogens to cellular stresses. Innate immune pathways provide the first line of defense against infections and endogenous threats. They sense microbial structures called pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) released from stressed or damaged cells and mount robust inflammatory responses. Autophagy is a fundamental process that maintains cellular homeostasis by performing multiple functions, including the turnover of damaged organelles and the killing of intracellular pathogens. While initially considered independent pathways, an overwhelming number of studies suggest dynamic crosstalk between these two cell-autonomous systems. Understanding this bidirectional communication will help in developing novel therapeutic strategies targeting infectious diseases, autoimmune disorders, and other immune-related pathologies. This review focuses on the multifaceted relationship between autophagy and innate immunity.

DOI: https://doi.org/10.1016/j.jmb.2025.169387
Cancer Treat Rev. 2025 Aug 11. pii: S0305-7372(25)00134-3. [Epub ahead of print]140 103012

Combining antibody-drug conjugates with immune checkpoint inhibitors: A new paradigm for breast cancer therapy.

Xiaoxiao Xu, Tong Yu, Zhenxing Wang.

  The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.

Keywords:  Antibody-drug conjugates; Combination; Immune checkpoint inhibitors; Oncology

DOI:  https://doi.org/10.1016/j.ctrv.2025.103012
Front Med (Lausanne). 2025 ;12 1572921

A roadmap for personalized medicine: the findings of the IC2PerMed project.

Flavia Beccia, Francesco Andrea Causio, Marzia Di Marcantonio, Ilda Hoxhaj, Chiara Cadeddu, Melissa Campagno, Lena Schleicher, Carmen Fotino, Maike Tauchert, Marta Lomazzi, Lili Wang, Wenya Wang, Huiyao Huang, Walter Ricciardi, Stefania Boccia.

   Introduction: Personalized Medicine (PM) tailors prevention and treatment to individuals based on their unique characteristics. It has the potential to improve health outcomes and healthcare sustainability by optimizing resource allocation. Both the European Union (EU) and China have prioritized PM in their health strategies. The IC2PerMed project was established to foster collaboration between the EU and China by developing a joint PM roadmap.
Methods: To assess the state of PM in the EU and China, the project conducted a comprehensive mapping of relevant policies, programs, funding mechanisms, and health ecosystems. Additionally, three Delphi surveys were carried out, identifying 65 priorities, which were synthesized into a set of strategic actions.
Results: The main output of the project is a joint roadmap for implementing PM in the EU and China. The roadmap promotes best practice exchange and addresses potential barriers to PM adoption. It outlines structural actions including enhancing health literacy, fostering intersectoral and international collaboration, ongoing review of emerging technologies, and facilitating innovation market entry through needs assessment and Health Technology Assessment. Key enablers such as data interoperability and shared standards are highlighted, along with ethical, social, and regulatory considerations that are universally relevant to PM implementation.
Discussion: A shared action plan can guide health policy and help policymakers understand the interconnection between healthcare, the economy, and society. By supporting international projects and investing in research and innovation, stakeholders can advance global healthcare.

Keywords:  China; European Union; personalized medicine; priorities; roadmap

DOI:  https://doi.org/10.3389/fmed.2025.1572921
BMC Med Inform Decis Mak. 2025 Aug 14. 25(1): 306

Process mining in healthcare: a tertiary study.

Adauto Santos, Gislaine Camila Lapasini Leal, Renato Balancieri.

  Business processes in healthcare are complex and multidisciplinary, involving various professional profiles and different healthcare structures, and each medical treatment may require distinct clinical pathways. Process mining can assist in discovering trajectories, verifying compliance, and enabling an understanding of the involvement of different organizational aspects. The main goal of this study is to provide a comprehensive overview of the application of process mining in healthcare. For this, a tertiary review was conducted, gathering 18 secondary reviews that addressed different aspects, such as the objectives of process mining in healthcare, types of activities and perspectives, available resources, primary medical specialties, types of medical processes, and limitations and challenges. The study reveals that process discovery is the most common activity, while the control flow was the most used perspective. The Heuristics Miner and Fuzzy Miner algorithms were the most relevant, and oncology was the medical specialty in which process mining was most used. Process mining has proven to be an effective tool for analyzing healthcare workflows, improving understanding of clinical guidelines and protocols, and supporting decision-making. However, it is necessary to deal with noisy or missing data and establish visualization mechanisms that ensure clarity in data presentation.

Keywords:  Clinical pathway; Healthcare process; Knowledge discovery; Process mining; Tertiary review

DOI:  https://doi.org/10.1186/s12911-025-02967-z
Cureus. 2025 Jul;17(7): e87688

A Bibliometric Analysis on Research Trends in Paediatric Epilepsy Treatment From 2005 to 2025.

Oliver Squires.

  The objective of this bibliometric analysis was to evaluate trends in paediatric epilepsy treatment research from 2005 to 2025. Through assessing which journals, countries, authors, and institutions have been the most productive and mapping trends in keywords used over time, the study aims to reveal emerging areas of interest and inspire ideas for future research. A total of 1418 relevant documents were retrieved from the Web of Science database. Documents outside of the target time period and non-English documents were excluded. From the 1152 remaining documents, 17 duplicates were removed using OpenRefine (OpenRefine). The final 1135 documents were then analysed using VosViewer (VOSviewer - Visualizing scientific landscapes) and Bibliometrix (https://www.bibliometrix.org/). The analysis revealed a stable number of annual global publications until a notable increase since 2018. The USA leads the way with the greatest research output (298 articles) and the highest number of total citations (6565). Harvard University emerged as the most productive institution (111 articles), whilst Epilepsia was the most productive journal (253 articles). Keyword co-occurrence analysis revealed a shift in research from earlier documents focusing more on traditional drug therapies to more recent articles focusing on cannabidiol based therapies, laser ablation, and vagal nerve stimulation. This bibliometric analysis provides new insights into the evolution of paediatric epilepsy treatment research. It helps to demonstrate the leading contributors in the field over the last 20 years, as well as highlighting emerging new trends. The results of the analysis underline the shift in the research away from more traditional treatments to investigating alternative therapies, including cannabidiol based therapies, dietary interventions, laser ablation, and vagal nerve stimulation. Through identifying these trends in the research and mapping author collaboration networks, it is hoped that this study can provide a foundational reference for researchers when planning future studies.

Keywords:  anti-epileptic; childhood; intervention; management; seizure; therapy

DOI:  https://doi.org/10.7759/cureus.87688
bioRxiv. 2025 Jul 15. pii: 2025.07.09.664005. [Epub ahead of print]

Using spatial statistics to infer game-theoretic interactions in an agent-based model of cancer cells.

Sydney Leither, Maximilian A R Strobl, Jacob G Scott, Emily Dolson.

Drug resistance in cancer is shaped not only by evolutionary processes but also by eco-evolutionary interactions between tumor subpopulations. These interactions can support the persistence of resistant cells even in the absence of treatment, undermining standard aggressive therapies and motivating drug holiday-based approaches that leverage ecological dynamics. A key challenge in implementing such strategies is efficiently identifying interaction between drug-sensitive and drug-resistant subpopulations. Evolutionary game theory provides a framework for characterizing these interactions. We investigate whether spatial patterns in single time-point images of cell populations can reveal the underlying game theoretic interactions between sensitive and resistant cells. To achieve this goal, we develop an agent-based model in which cell reproduction is governed by local game-theoretic interactions. We compute a suite of spatial statistics on single time-point images from the agent-based model under a range of games being played between cells. We quantify the informativeness of each spatial statistic and demonstrate that a simple machine learning model can classify the type of game being played. Our findings suggest that spatial structure contains sufficient information to infer ecological interactions. This work represents a step toward clinically viable tools for identifying cell-cell interactions in tumors, supporting the development of ecologically informed cancer therapies.
Author summary: Drug resistance is a major challenge in cancer treatment, often leading to relapse despite initially successful therapy. While mutations are a key driver, ecological interactions between drug-sensitive and drug-resistant cells also play a critical role. These interactions are complex and dynamic, and few molecular biomarkers exist, making them difficult to study and account for in treatment planning. We use evolutionary game theory, a framework for quantifying interactions between cells, to investigate whether it is possible to infer these interactions using just a single time-point image of the cells. We develop an agent-based model where cells reproduce based on local interactions and quantify the resulting patterns in how cells are distributed across space using a suite of spatial statistics. We find that specific interaction types produce distinct spatial patterns that are evident in these metrics, and we train a simple machine learning model to classify the interaction type based on the metrics. Our results suggest that spatial data alone can offer valuable insights into tumor dynamics, potentially enabling more informed and adaptable cancer treatments based on eco-evolutionary principles.

DOI: https://doi.org/10.1101/2025.07.09.664005