Multimodal cancer immunotherapy is a combination of cancer immunotherapies used to treat cancer in patients. T cell receptor diversity is used as a component of a method to treat cancer involving cancer therapy, including multimodal cancer immunotherapy.

As described below, the present invention features genetically modified immune cells having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft versus host reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

As described below, the present invention features genetically modified immune cells having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft versus host reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

This invention relates to genetic engineering, in particular to an insertion site for a transgene, cells comprising a transgene or other modification at that insertion site, vectors for targeting that insertion site, and methods for creating transgenic cells by insertion or other modification at that site. The insertion site, or “safe harbour locus”, is identified within the SPATA13 gene on human chromosome 13q12.12. Mammalian cells comprising a genetic modification within the SPATA13 gene on chromosome 13q12.12 are described, wherein the modification may be an insertion such as an integrated transgene. Nucleic acid molecules able and adapted to guide the insertion of a transgene to that insertion site are also described. These cells or nucleic acids may be useful in therapy.

This invention relates to genetic engineering, in particular to an insertion site for a transgene, cells comprising a transgene or other modification at that insertion site, vectors for targeting that insertion site, and methods for creating transgenic cells by insertion or other modification at that site. The insertion site, or “safe harbour locus”, is identified within the SPATA13 gene on human chromosome 13q12.12. Mammalian cells comprising a genetic modification within the SPATA13 gene on chromosome 13q12.12 are described, wherein the modification may be an insertion such as an integrated transgene. Nucleic acid molecules able and adapted to guide the insertion of a transgene to that insertion site are also described. These cells or nucleic acids may be useful in therapy.

Compositions for and methods of manufacturing a fucosylated cell population are provided. The method may include expansion of the cells and/or cryopreservation of the cells under conditions that retain optimum levels of cell surface fucosylation.

Compositions for and methods of manufacturing a fucosylated cell population are provided. The method may include expansion of the cells and/or cryopreservation of the cells under conditions that retain optimum levels of cell surface fucosylation.

Disclosed herein include methods and compositions for incorporating an effector gene into the genome of a cell. The method can comprise introducing into a cell a donor nucleic acid comprising a recognition site, a splice acceptor site, a self-cleaving peptide sequence, an effector gene, and an optional transcript stabilization element. The donor nucleic acid can be incorporated into the intron of a target gene differentially expressed in a unique cell type and/or in a cell during a unique cell state via non-homologous end joining (NHEJ)-dependent DNA repair. There are also provided, in some embodiments, methods and compositions for treating a disease or disorder in a subject.

Disclosed herein include methods and compositions for incorporating an effector gene into the genome of a cell. The method can comprise introducing into a cell a donor nucleic acid comprising a recognition site, a splice acceptor site, a self-cleaving peptide sequence, an effector gene, and an optional transcript stabilization element. The donor nucleic acid can be incorporated into the intron of a target gene differentially expressed in a unique cell type and/or in a cell during a unique cell state via non-homologous end joining (NHEJ)-dependent DNA repair. There are also provided, in some embodiments, methods and compositions for treating a disease or disorder in a subject.

A method and a system for image-guided intervention such as a percutaneous treatment or diagnosis of a patient may include at least one of a pre-registration method and a re-registration method. The pre-registration method is configured to permit for an efficient virtual representation of a planned trajectory to target tissue during the intervention, for example, as a holographic light ray shown through an augmented reality system. In turn, this allows the operator to align a physical instrument such as a medical probe for the intervention. The re-registration method is configured to adjust for inaccuracy in the virtual representation generated by the pre-registration method, as determined by live imaging of the patient during the intervention. The re-registration method may employ the use of intersectional contour lines to define the target tissue as viewed through the augmented reality system, which permits for an unobstructed view of the target tissue for the intervention.