Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

A method for treating tumors using a combination of an oncolytic virus vaccine and immune cells. The method specifically includes the following step: treating the tumors by using a combination of the immune cells and the oncolytic virus vaccine; the oncolytic virus vaccine includes a recombinant oncolytic virus expressing a tumor antigen and is used for targeting the tumor cells; the immune cells express a chimeric antigen receptor paired with the tumor antigen, and are used for killing or destroying the tumor cells targeted; the recombinant oncolytic virus includes an M protein, G protein, N protein, P protein and L protein subjected to site-directed mutagenesis. The tumor antigen expressed by the oncolytic virus vaccine can guide the immune cells to reach the target tumor tissue center, achieving a curative effect where 1+1 is greater than 2, with a tumor cell killing rate being up to 100% at most.