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| http://dx.doi.org/10.1016/j.ymthe.2024.03.017 | DOI Listing |
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Proteolysis targeting chimera (PROTAC)-driven antibody internalization of oncogenic cell surface receptors.
Commun Biol
December 2024
Mayo Clinic, Rochester, MN, USA.
Antibody-drug conjugates (ADCs) are increasingly used in clinic for multiple indications and may improve upon the activity of parental antibodies by delivering cytotoxic payloads into target cells. This activity is predicated upon internalization to release the cytotoxic payloads intracellularly. Since binding of ADCs to their cell surface targets does not guarantee their internalization, we hypothesize that proteolysis targeting chimeras (PROTACs) could improve the activity of ADCs through forced internalization.
View Article and Find Full Text PDFDurable antitumor response via an oncolytic virus encoding decoy-resistant IL-18.
J Immunother Cancer
December 2024
State Key Laboratory of Biotechnology, Medical School, Nanjing University, Nanjing, China
Article Synopsis
- Interleukin-18 (IL-18) enhances immune responses, but its clinical use is limited by a decoy receptor; to overcome this, researchers developed a variant called DR18 that doesn't bind to IL-18 binding protein.
- They tested this DR18 variant using an oncolytic adenovirus (oAdDR18) in mouse models of different tumors to see its effects on tumor growth and immune response.
- Results showed that oAdDR18 led to significant tumor growth reduction and enhanced immune cell infiltration compared to other forms of IL-18, indicating strong potential for treating cancers and reducing metastasis.
IL-12 encoding oNDV synergizes with CAR-T cells in orthotopic models of non-small cell lung cancer.
Mol Ther Oncol
December 2024
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells.
View Article and Find Full Text PDFBioorthogonal oncolytic-virus nanovesicles combined bio-immunotherapy with CAR-T cells for solid tumors.
Biomater Sci
November 2024
Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China.
Various oncolytic viruses (OVs) have been adopted as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-T cells against solid tumors. However, the therapeutic effect of OVs has been limited by pre-existing neutralizing antibodies and poor targeting delivery for systemic administration. Herein, we propose using bioorthogonal OV nanovesicles to boost the antitumor effects of CAR-T cells in solid tumors by reshaping the tumor microenvironment.
View Article and Find Full Text PDFImmune checkpoint inhibitors for glioblastoma: emerging science, clinical advances, and future directions.
J Neurooncol
November 2024
Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
Glioblastoma (GBM), the most common and aggressive primary central nervous system (CNS) tumor in adults, continues to have a dismal prognosis. Across hundreds of clinical trials, few novel approaches have translated to clinical practice while survival has improved by only a few months over the past three decades. Randomized controlled trials of immune checkpoint inhibitors (ICIs), which have seen impressive success for advanced or metastatic extracranial solid tumors, have so far failed to demonstrate a clinical benefit for patients with GBM.
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