On Feburary 2nd, 2024, the team lead by Yuan Ping of CPS-ZJU from National Key Laboratory of Advanced Drug Delivery System published a paper on Nature Biotechnology, titled An oncolytic virus-T cell chimera for cancer immunotherapy, which develops a type of delivery technique called ONCOTECH to enhance the targeted delivery of oncolytic virus and improve tumor microenvironment.

The technique begins with the construction of a oncolytic virus adenovirus expressing CRISPR/Cas9, which is membrane-encapsulated by using a biofilm containing a specific antigen expression, then edits the oncolytic virus named eOA via membrane-encapulated genes carried by T cell receptors on the surface of T cells. The research finds out that T cells can reinforce the targeted delivery of solid tumors by eOA, improve the tumor microenvironment through intratumoral gene editing of the PD-L1 gene, and enhance the efficacy of both oncolytic virus therapy and relay T cell therapy in solid tumor treatment. To further push clinical transformation, the team upgrades the ONCOTECH technique, where HEK293 cells expressing specific antigens are used to prepare the vesicles containing gene-edited oncolytic virus, which are carried to the surface of CAR-T cells with specific antigens. The efficacy of the system is further validated, and even proved better than employing oncolytic virus or T cells alone, in a human in situ brain tumor model, a human in situ lung cancer, and a human pancreatic PDX model using humanized mice with human immune systems. Besides, ONCOTECH is also capable of inducing long-term immune memory in tumors, preventing tumor recurrence.

More information: Yuan Ping, Professor of CPS-ZJU, is the corresponding author, Yuxuan Chen and Xiaohong Chen, both doctors of CPS-ZJU, are the first authors, while collaborators include Wei Wei, researcher of Institute of Process Engineering, Chinese Academy of Sciences, and Gang Liu, Professor of Xiamen University.

Translator: Zihao Liu

Editor: Yichen Zhu