Journal
CLINICAL & TRANSLATIONAL IMMUNOLOGY
Volume 9, Issue 6, Pages -Publisher
WILEY
DOI: 10.1002/cti2.1137
Keywords
anaplastic meningioma; B7-H3; chimeric antigen receptor; immunotherapy
Categories
Funding
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2019ZX09301-147]
- Major Subject of the Science and Technology Department of Sichuan Province [2017SZ0015]
- Double Top Construction and Innovation Spark Item of Sichuan University [2082604401047]
- 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYJC18007]
- Incubation project of clinical study, West China Hospital, Sichuan University [2019HXFH020]
Ask authors/readers for more resources
Objective We conducted a first-in-human study to evaluate the bioactivity and safety of B7-H3-targeted chimeric antigen receptor (CAR) autologous T cells for treating recurrent anaplastic meningioma. Methods Tumor tissues from a patient with recurrent anaplastic meningioma were evaluated for B7-H3 expression. B7-H3-targeted CAR-T cells were delivered into the intracranial tumor resection cavity using an Ommaya device at a maximum dose of 1.5 x 10(7) cells. Magnetic resonance imaging (MRI) screening and multiple serum indexes were regularly monitored. The patient received surgical intervention after three-cycle infusions, allowing analysis for CAR-T-cell infiltration and target antigen expression in post-CAR-T therapy tumor tissues. Results Immunochemical analysis demonstrated high and homogeneous B7-H3 expression in tumor samples. MRI results indicated that the tumor near the delivery device was relatively stable compared with the rapid progression of tumors distant from the device. We found CAR-T-cell trafficking to regions of B7-H3(+)tumor tissues near the device, but not to tumor tissues distant from the device. Decreased B7-H3 expression was observed near the region of CAR-T-cell infiltration after therapy. The intracavitary delivery of B7-H3-targeted CAR-T cells was well-tolerated and not associated with any toxic effects of grade 3 or higher. Conclusion Our results suggested that although intracavitary administration of B7-H3-targeted CAR-T cells was safe and resulted in local bioactivity, addressing antigen loss and CAR-T-cell trafficking may further enhance the applications of B7-H3-targeted CAR-T-cell therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available