Asset Details
Do you wish to reserve the book?
A high-content screen identified ingenol-3-angelate as an enhancer of B7-H3-CAR T cell activity by increasing B7-H3 protein expression on the target cell surface via PKCα activation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A high-content screen identified ingenol-3-angelate as an enhancer of B7-H3-CAR T cell activity by increasing B7-H3 protein expression on the target cell surface via PKCα activation
Do you wish to request the book?
A high-content screen identified ingenol-3-angelate as an enhancer of B7-H3-CAR T cell activity by increasing B7-H3 protein expression on the target cell surface via PKCα activation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Paper
A high-content screen identified ingenol-3-angelate as an enhancer of B7-H3-CAR T cell activity by increasing B7-H3 protein expression on the target cell surface via PKCα activation
2023
Overview
CAR T cell therapy is a promising approach to improve outcomes and decrease toxicities for patients with cancer. While extraordinary success has been achieved using CAR T cells to treat patients with CD19-positive malignancies, multiple obstacles have so far limited the benefit of CAR T cell therapy for patients with solid tumors. Novel manufacturing and engineering approaches show great promise to enhance CAR T cell function against solid tumors. However, similar to single agent chemotherapy approaches, CAR T cell monotherapy may be unable to achieve high cure rates for patients with difficult to treat solid tumors. Thus, combinatorial drug plus CAR T cell approaches may ultimately be required to achieve widespread clinical success. In this regard, we developed a novel high-content and high-throughput screen to evaluate 1114 FDA approved drugs to increase expression of the solid tumor antigen B7-H3 in metastatic osteosarcoma cells. In this proof-of-principle screen, we demonstrate that ingenol-3-angelate increased B7-H3 (CD276) mRNA, total protein, and cell surface expression. Mechanistically, ingenol-3-angelate increased B7-H3 expression via protein kinase C alpha activation. Functionally, ingenol-3-angelate induced B7-H3 expression enhanced B7-H3-CAR T cell function, highlighting utility of the approach, and paving the way for expanding this high-throughput and high-content technique to study other tumor and CAR T cell combinations.
Publisher
Cold Spring Harbor Laboratory
Subject
