Abstract: The present disclosure relates to chimeric antigen receptor (CAR) expressing immune effector cells showing highly specific and sensitive recognition of CLDN6 expressing cancer cells as well as a high potential for treating cancer in humans.

Abstract: The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8? targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8+ T cells in vitro and in vivo.

Abstract: The present disclosure relates to methods for enhancing the efficiency of therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells, even when provided to a subject in sub-therapeutic amounts, are extremely effective in the treatment of cancer diseases, even those cancer diseases that are known to be difficult to treat with antigen receptor-engineered immune effector cells, such as solid tumors or cancers, if additionally target antigen for the antigen receptor is provided to the subject. Immune effector cells may be engineered ex vivo or in vitro and subsequently the immune effector cells may be administered to a subject in need of treatment, or immune effector cells may be engineered in vivo in a subject in need of treatment.

Abstract: The present disclosure relates to a chimeric antigen receptor (CAR) showing highly specific and sensitive recognition of CLDN6 expressing target cells as well as a high potential for survival and repetitive stimulation of CAR T cells.

Abstract: The present disclosure relates to methods and agents for enhancing the effect of T cells engineered to express chimeric antigen receptors (CARs). These methods and agents are, in particular, useful for the treatment of diseases characterized by diseased cells expressing an antigen the CAR is directed to. Specifically, the present disclosure relates to methods comprising providing to a subject T cells genetically modified to express a chimeric antigen receptor (CAR) and administering to the subject IL2 or a polynucleotide encoding IL2. The methods of the disclosure may comprise administering IL2 or a polynucleotide encoding IL2 and a further cytokine or a polynucleotide encoding a further cytokine, wherein the further cytokine may be IL7 or IL21. The T cells genetically modified to express a CAR may be provided to the subject by administering the T cells genetically modified to express a CAR or by generating the T cells genetically modified to express a CAR in the subject.