In a first aspect, the present disclosure relates to genetically modified T-cells having a chimeric antigen receptor for use in adoptive cell therapy for treating CD30+ cancer in a subject need thereof. In particular, the present disclosure relates to a T-cell containing a specific chimeric antigen receptor being toxic to CD30+cancer cells while being non-toxic to CD30+ non-cancer cells. In a further aspect, the present disclosure relates to a specific chimeric antigen receptor and the nucleic acid molecule encoding the receptor as well as vectors and cells containing the same. Finally, the present disclosure relates to the use of the chimeric antigen receptor for use in improving persistence and amplification of lymphocyte containing the same and the use of specific peptides for improving persistence and amplification of genetically modified lymphocytes expressing the same.

The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).

The disclosure provides immune cells comprising a first activator receptor specific to CEA, and a second inhibitory receptor, and methods of making and using same for the treatment of cancer.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

A chimeric antibody receptors with anti-cotinine antibodies linked, and uses thereof are disclosed. A T cell presenting the chimeric antibody receptor on the surface secretes interferon gamma specifically for a target molecule of a cotinine-conjugated binding molecule that is added together therewith and induces cell death of the cell expressing the target molecule by the T cell. On the contrary, by administering a cytotoxic agent conjugated with cotinine, cell death of the chimeric antigen receptor T cell is induced. Therefore, if necessary, a cytotoxic agent conjugated with cotinine can be administered to remove the chimeric antigen receptor T cells that have been already administered, thereby suppressing immune side effects due to hyperactivity of T cells. Thus, the chimeric antigen receptor to which the anti-cotinine antibody is linked can be effectively and safely used for the treatment of cancer.

The risk with introducing manipulated T-cell is unforeseen adverse events. During the development of chimeric antigen receptor (CAR) T-cell therapies almost all clinical trial has shown some adverse events ranging from cytokine mediated toxicities to tissue damage and death. By the present invention, we aim to induce multiple layers of safety checkpoints. As a last resort we will be able to induce suicide in all cells which we have introduced to the body. Here we describe the scientific background to the parts of our suicide switch and the details regarding the proteins which are included. Safety switches are being tested on CAR-T cells, but they have a few drawbacks. Due to the limited space on the CAR vector, there is only room for one gene switch. Presently the results show they induce apoptosis in around 70-90% of cells, while the desired target is for all cells to be removed from the tissue. By utilising the space available on a synthetic chromosome, we can include multiple genes under Tet operons which allow us to turn multiple genes on/off. Life or death of a cell depends on the balance of the pro and anti-apoptotic proteins. The scale is always shifting a bit back and forth but only when tipped completely over the apoptotic cascade is initiated. By fine tuning the balance we aim to ensure that the hSync carrying cells have a survival advantage in the tumour in the absence of inducing agent. On the other hand, the moment that agent is administrated the cells will undergo apoptosis and express find me and eat me markers making sure they are removed without risk of tissue damage. The present invention encompasses compositions and methods for use in cellular gene therapeutics using a modular approach to genetically engineer cells to carry a synthetic chromosome having a regulatable system including one or more safety switches.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Modified immune cells expressing a heterodimeric gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) are described. The disclosed modified immune cells enhance expression of CARs. Also disclosed are compositions and methods for making such cells, and use of such cells in treating disease.

Contemplated cancer therapies comprise co-administration of aldoxorubicin with an immune therapeutic composition that preferably comprises a vaccine component and a cytotoxic cell component.

Provided herein are antibodies (e.g., sdAb such as VHH) specifically binding to CEACAM5, constructs and conjugates comprising the antibodies, and methods of making and uses thereof.