The Vascular Disrupting Agent CA4P Improves the Antitumor Efficacy of CAR-T Cells in Preclinical Models of Solid Human Tumors
| Autor: | Junshuang Gao, Jixiang Cao, Jiebin Dong, Shixin Zhou, Hongkui Deng, Yun Bai, Jingjing Zhao, Changwen Deng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Mice
SCID Immunotherapy Adoptive 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Mouse xenograft Mice Inbred NOD Ovarian carcinoma Drug Discovery Stilbenes Genetics Medicine Animals Humans Molecular Biology 030304 developmental biology Pharmacology Combretastatin Ovarian Neoplasms 0303 health sciences Receptors Chimeric Antigen business.industry medicine.disease HCT116 Cells Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Chimeric antigen receptor Tumor Burden HEK293 Cells Treatment Outcome chemistry A549 Cells 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Molecular Medicine Original Article Female Combretastatin A-4 phosphate Car t cells business Ovarian cancer Infiltration (medical) human activities |
| Zdroj: | Mol Ther |
| Popis: | Chimeric antigen receptor (CAR) T cell therapy remains relatively ineffective against solid tumors due to inadequate infiltration and in vivo expansion of CAR-T cells. Unlike hematological malignancies, solid tumors have vascular barriers that hinder CAR-T cells from reaching the tumor site. Here, we demonstrated that combretastatin A-4 phosphate (CA4P), a vascular disrupting agent (VDA), can significantly improve the infiltration ability of CAR-T cells in solid tumors as evidenced by elevated levels of IFN-γ. Moreover, combined treatment with CA4P and CAR-T cells greatly increased the therapeutic efficiency of the CAR-T cells in subcutaneous ovarian cancer mouse xenograft models and patient-derived xenograft (PDX) models of colon and ovarian carcinoma. Our findings highlight CA4P as an effective antitumor agent candidate for combination with CAR-T cells in clinical applications to treat solid tumors. |
| Databáze: | OpenAIRE |
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