Abstract: A chimeric antigen receptor including: a binding domain, the full DAP 10 protein, the full DAP 12 protein, or a functional variant thereof, and a hook binding domain. Also, a vector system comprising one or more vector including: a nucleic acid comprising a nucleic acid sequence encoding a chimeric antigen receptor and optionally a nucleic acid encoding a hook fusion protein, preferably having a streptavidin core; wherein the nucleic acids are located on the same or on different vectors. Further, a lentiviral vector particles system, host cell and kit including the nucleic acids or vector system, and their use as a medicament, notably for immunotherapy.

Abstract: A hook fusion protein, which includes a hook domain and at least one cytoplasmic carboxyl endoplasmic reticulum (ER) retention signal and/or at least one cytoplasmic amino terminal endoplasmic reticulum (ER) retention signal; wherein the hook fusion protein is a soluble protein that localizes in the cytoplasm. Also, a nucleic acid system for intracellular targeting control including a nucleic acid encoding a target fusion protein including a hook fusion protein, and a nucleic acid encoding a target fusion protein including a hook-binding domain; wherein the target fusion protein is a membrane protein; and wherein the hook fusion protein localizes in the ER when bound to the target fusion protein. Additionally, a vector system, viral particle system, host cell and kit include these nucleic acids. Further, the vector system, viral particle system, host cell or kit for use as a medicament, in particular for immunotherapy.

Abstract: The present invention relates to a chimeric antigen receptor comprising: a binding domain, the full DAP 10 protein, the full DAP 12 protein, or a functional variant thereof, anda hook binding domain.The present invention also relates to a vector system comprising one or more vector comprising: a nucleic acid comprising a nucleic acid sequence encoding a chimeric antigen receptor and optionally a nucleic acid encoding a hook fusion protein, preferably comprising a streptavidin core; wherein said nucleic acids are located on the same or on different vectors; The invention also encompasses lentiviral vector particles system, host cell and kit comprising said nucleic acids or vector system. The invention also relates to lentiviral vector particles system, host cell and kit as herein disclosed for their use as a medicament, notably for immunotherapy.

Abstract: The present invention relates to a hook fusion protein comprising a hook domain and at least one cytoplasmic carboxy terminal endoplasmic reticulum (ER) retention signal and/or at least one cytoplasmic amino terminal endoplasmic reticulum (ER) retention signal; wherein the hook fusion protein is a soluble protein that localizes in the cytoplasm. The present invention also relates to a nucleic acid system for intracellular targeting control comprising a nucleic acid encoding a hook fusion protein as herein disclosed, and a nucleic acid encoding a target fusion protein comprising a hook-binding domain; wherein said target fusion protein in a membrane protein; and wherein the hook fusion protein localizes in the ER when bound to the target fusion protein. The invention also encompasses a vector system, viral particle system, host cell and kit comprising said nucleic acids.