bims-carter 2025-07-20 papers

Issue of 2025–07–20
four papers selected by
Luca Bolliger, lxBio

Math Biosci Eng. 2025 May 21. 22(7): 1653-1679

Optimal therapy schedule of chimeric antigen receptor (CAR) T cell immunotherapy.

Chimeric antigen receptor (CAR) T-cell therapy is a personalized immunotherapy approach in which a patient's T cells are genetically engineered to express synthetic receptors that specifically recognize and target tumor-associated antigens. This approach has demonstrated remarkable success in treating B-cell malignancies by directing CAR-T cells against the CD19 protein. However, treatment efficacy is influenced by the composition and distribution of CAR-T cell subsets administered to the patient. To investigate the impact of different CAR-T cell subtypes and infusion strategies, we developed a mathematical model that captures the dynamic interactions between tumor cells and CAR-T cells within the tumor immune microenvironment. Through computational simulations, we explored how varying the dosage and subtype proportions of infused CAR-T cells affects tumor dynamics and therapeutic outcomes. Our findings highlight the critical role of CAR-T cell subset composition in optimizing treatment efficacy, underscoring the necessity of precise dosing control and tailored infused strategies to maximize therapeutic success.

Keywords: B-ALL ; CAR-T therapy ; mathematical model ; optimal therapy ; tumor-immune microenvironment

DOI: https://doi.org/10.3934/mbe.2025061

Curr Opin Hematol. 2025 Jul 15.

Advances in chimeric antigen receptor-T therapies to target tumor resistance in B-cell malignancies.

Nassim Salem, Mohamad Hamieh.

PURPOSE OF REVIEW: Chimeric Antigen Receptor T cell (CAR-T) has transformed B-cell malignancies treatment, with seven FDA-approved therapies to date. Despite remarkable success, a substantial fraction of patients relapse, primarily due to limited CAR-T persistence or tumor escape driven by target-antigen loss. Here, we highlight preclinical and clinical advances in programming T cells to address these challenges and are poised to drive next-generation CAR-T development.
RECENT FINDINGS: Building on FDA-approved CAR designs, innovations in tailoring CAR signaling, cytokine armoring, and multiantigen targeting are paving the way toward more effective and safer treatments. Satisfyingly, these new approaches have demonstrated feasibility, safety, and promising clinical activity, including in patients relapsing after prior CAR treatment. In parallel, CARs with enhanced sensitivity to low-antigen tumors are advancing from preclinical to clinical development. These innovations aiming to enhance T cell persistence and counter tumor escape are defining the next wave of CAR therapies.
SUMMARY: Here, we outline key advances in CAR-T programming to improve persistence, broaden antigen targeting, and enhance efficacy in B-cell malignancies. While challenges such as toxicities or identifying optimal and standardized approaches across trials remain to be addressed, these approaches provide a foundation for translating innovations into effective and potentially curative CAR immunotherapies.

Keywords: B-cell malignancies; TCR-like chimeric antigen receptor; antigen escape; chimeric antigen receptor-T cell; multiantigen targeting; tumor resistance

DOI: https://doi.org/10.1097/MOH.0000000000000892

Int J Mol Sci. 2025 Jun 29. pii: 6290. [Epub ahead of print]26(13):

Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.

Carina A Doeppner, Amanda Katharina Binder, Franziska Bremm, Niklas Feuchter, Jan Dörrie, Niels Schaft.

Cancer remains one of the leading causes of death worldwide. New treatments like immunotherapy-especially checkpoint inhibitors and CAR-T cell therapy-have improved outcomes for some patients. However, these therapies often struggle to treat solid tumours effectively. Natural killer (NK) cells are part of the immune system and can naturally detect and destroy cancer cells without previous adaption. Scientists are now enhancing these cells by adding special receptors, called CARs (chimeric antigen receptors), to help them better recognize and attack cancer, an approach originally developed for T cells. CAR-NK cell therapy has some advantages over CAR-T therapy. It tends to cause fewer severe side effects, such as strong immune reactions or off-target effects in healthy tissues. Within some limitations, the allogenic use of CAR-NK cells is possible, as these cells exert less graft-versus-host activity. Such CAR-NK cell products can be produced in larger quantities and stored, making treatment more accessible. Still, there are challenges. It can be difficult to create enough modified NK cells, and the tumour microenvironment can block their activity. This review highlights recent progress in CAR-NK therapy, including early lab and clinical research. It also explores ways to improve these treatments and how they might work alongside other cancer therapies to help more patients in the future.

Keywords: CAR-NK cells; adoptive cell therapy; chimeric antigen receptors (CAR); clinical application; combination therapy; immunotherapy; solid tumours; tumour microenvironment

DOI: https://doi.org/10.3390/ijms26136290

Front Immunol. 2025 ;16 1622433

CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.

Wan-Ying Zhang, Lang-Yu Yang, Xing-Xing Fan.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment landscape for hematologic malignancies; however, its efficacy in solid tumors remains limited due to antigen heterogeneity, a suppressive tumor microenvironment, and tumor-intrinsic resistance mechanisms. In parallel, immune checkpoint blockade (ICB) therapies have achieved clinical milestones but often fail due to impaired antigen presentation, interferon signaling dysregulation, and immune exclusion. Recent advances in CAR-T therapy-based technologies including multi-specific and armored CAR constructs, gene-editing strategies, and synthetic circuits offer new opportunities to overcome these barriers and expand therapeutic efficacy. Artificial intelligence (AI) has further accelerated the discovery of novel tumor antigens, optimized CAR design, and enabled real-time modeling of treatment responses. Integration of CAR-T therapy with AI-driven platforms, metabolic reprogramming, bispecific antibodies, and advanced single-cell analytics represents a powerful strategy to enhance tumor targeting and durability of response. This review summarizes emerging CAR-T therapy-based innovations, explores their synergistic applications with immunotherapies, and discusses current challenges related to safety, manufacturing, cost, and biomarker validation. These multidisciplinary efforts collectively pave the way toward more effective and personalized cancer treatment.

Keywords: artificial intelligence; car-t; immunity; tumor; tumor microenvironment

DOI: https://doi.org/10.3389/fimmu.2025.1622433