Rationally designed approaches to augment CAR-T therapy for solid tumor treatment

Zhu, Chaojie; Wu, Qing; Sheng, Tao; Shi, Jiaqi; Shen, Xinyuan; Yu, Jicheng; Du, Yang; Sun, Jie; Liang, Tingxizi; He, Kaixin; Ding, Yuan; Li, Hongjun; Gu, Zhen; Wang, Weilin

doi:10.1016/j.bioactmat.2023.11.002

Cited by 5 publications

(4 citation statements)

References 151 publications

(171 reference statements)

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“…By leveraging the specificity of CAR-T cells, these approaches hold the promise of enhanced efficacy with reduced off-target effects. As the field continues to explore novel antigens and optimize CAR-T cell engineering, the potential for further innovations in chordoma therapy becomes increasingly apparent [43,44].…”

Section: Car-t Cell Therapymentioning

confidence: 99%

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

Agosti,

Antonietti,

Zeppieri

et al. 2024

JCM

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Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “chordomas”, “molecular biology”, “gene aberrations”, and “target therapies”. The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

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Section: Car-t Cell Therapymentioning

confidence: 99%

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

Agosti,

Antonietti,

Zeppieri

et al. 2024

JCM

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“…Adjuvant CAR-NK Cell Therapy: Post-surgical application of CAR-NK cells could play a pivotal role in eradicating residual malignant cells that evade surgical excision [108]. This could be particularly beneficial in the context of microscopic residual disease, which often contributes to cancer recurrence.…”

Section: Future Research Directions and Challengesmentioning

confidence: 99%

CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges

Li,

Wang,

Zhang

et al. 2024

Preprint

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The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

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“…Lastly, researchers must embrace new methods and continue to explore the strategies discussed in this review. To further advance tissue engineering and regenerative medicine, it's necessary to consider laser-induced modification of biomaterials and treatments [ 187 ], CAR T cell-mediated treatments [ 188 ], CRISPR-powered techniques [ 189 ], 3D printing for advanced biomaterials, and multi-omics analysis [ 190 ]. These innovative approaches can potentially overcome current limitations and significantly enhance the effectiveness of regenerative therapies.…”

Section: Prospectsmentioning

confidence: 99%

Fostering tissue engineering and regenerative medicine to treat musculoskeletal disorders in bone and muscle

Park,

Rahaman,

Kim

et al. 2024

Bioactive Materials

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Rationally designed approaches to augment CAR-T therapy for solid tumor treatment

Cited by 5 publications

References 151 publications

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges

Fostering tissue engineering and regenerative medicine to treat musculoskeletal disorders in bone and muscle

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