Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors DOI Creative Commons
Bo Zou, Mengge Wang, Shimeng Bai

и другие.

Biomedicines, Год журнала: 2025, Номер 13(4), С. 844 - 844

Опубликована: Апрель 1, 2025

Background/Objectives: The AXL receptor tyrosine kinase is a promising therapeutic target in solid tumors, yet conventional viral vector-engineered CAR-T cells face critical limitations, including risks of insertional mutagenesis and immunogenicity from murine-derived single-chain variable fragments (scFvs). This study aimed to develop evaluate mRNA-engineered fully human (mfhAXL CAR-T) as safer, scalable alternative for tumor immunotherapy. Methods:mfhAXL were generated via electroporation-mediated delivery vitro transcribed mRNA encoding AXL-specific CAR. CAR expression kinetics T-cell viability quantified by flow cytometry. Antitumor activity was assessed through co-cultures with AXL-positive lung pancreatic cancer cells, measuring cytotoxicity, cytokine secretion, specificity. In vivo efficacy evaluated xenograft mouse model, volume body weight monitored over 14 days. Results: Flow cytometry confirmed transient but high (>90% at 24 h) preserved (>90%). vitro, mfhAXL exhibited dose-dependent cytotoxicity antigen-specific secretion. vivo, four administrations suppressed growth without loss. Conclusions: mRNA-electroporated platform enables cost-effective, large-scale production, offering safer vector-based approaches eliminating immunogenicity.

Язык: Английский

Tumor-Agnostic Therapies in Practice: Challenges, Innovations, and Future Perspectives DOI Open Access
Sulin Wu, Rajat Thawani

Cancers, Год журнала: 2025, Номер 17(5), С. 801 - 801

Опубликована: Фев. 26, 2025

This review comprehensively analyzes the current landscape of tumor-agnostic therapies in oncology. Tumor-agnostic are designed to target specific molecular alterations rather than primary site tumor, representing a shift cancer treatment. We discuss recent approvals by regulatory agencies such as FDA and EMA, highlighting that have demonstrated efficacy across multiple types sharing common alterations. delve into trial methodologies underpin these approvals, emphasizing innovative designs basket trials umbrella trials. These present unique advantages, including increased efficiency patient recruitment ability assess drug diverse populations rapidly. However, they also entail certain challenges, need for robust biomarkers complexities requirements. Moreover, we examine promising prospects developing rare cancers exhibit targets typically associated with more prevalent malignancies. By synthesizing insights, this underscores transformative potential It offers pathway personalized treatment transcends conventional histology-based classification.

Язык: Английский

Процитировано

0
Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology DOI Creative Commons
Shuang Ma, Ying Lü,

S.J. Sui

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides comprehensive review of methodologies for evaluating including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, single-fiber experiments to assess quality performance. Furthermore, it elucidates mechanisms, applications, limitations various modalities, immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, combined chemoimmunotherapy, while examining their effects on function systemic responses. Key findings indicate that although is effective in augmenting antitumor immunity, frequently induces muscle-related adverse such as weakness, fatigue, or damage, primarily mediated by cytokine release activation. underscores significance niches within microenvironment influencing treatment outcomes proposes strategies optimize therapy through personalized regimens combinatorial approaches. highlights need further formation interactions muscle-tumor. Our crucial advancing efficacy immunotherapy, reducing effects, ultimately improving survival rates life patients with cancer.

Язык: Английский

Процитировано

0
Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors DOI Creative Commons
Bo Zou, Mengge Wang, Shimeng Bai

и другие.

Biomedicines, Год журнала: 2025, Номер 13(4), С. 844 - 844

Опубликована: Апрель 1, 2025

Background/Objectives: The AXL receptor tyrosine kinase is a promising therapeutic target in solid tumors, yet conventional viral vector-engineered CAR-T cells face critical limitations, including risks of insertional mutagenesis and immunogenicity from murine-derived single-chain variable fragments (scFvs). This study aimed to develop evaluate mRNA-engineered fully human (mfhAXL CAR-T) as safer, scalable alternative for tumor immunotherapy. Methods:mfhAXL were generated via electroporation-mediated delivery vitro transcribed mRNA encoding AXL-specific CAR. CAR expression kinetics T-cell viability quantified by flow cytometry. Antitumor activity was assessed through co-cultures with AXL-positive lung pancreatic cancer cells, measuring cytotoxicity, cytokine secretion, specificity. In vivo efficacy evaluated xenograft mouse model, volume body weight monitored over 14 days. Results: Flow cytometry confirmed transient but high (>90% at 24 h) preserved (>90%). vitro, mfhAXL exhibited dose-dependent cytotoxicity antigen-specific secretion. vivo, four administrations suppressed growth without loss. Conclusions: mRNA-electroporated platform enables cost-effective, large-scale production, offering safer vector-based approaches eliminating immunogenicity.

Язык: Английский

Процитировано

0