The present invention relates to a method and system for identifying and validating pairs of candidate antigens and their cognate antigen-specific T lymphocytes that are useful for validating the immunogenic activity of paired antigen and TCR sequences. The method includes, inter alia, steps of determining one or more splice variants that are more highly transcribed in a sample obtained e from cohort of patients compared to a reference sample, determining one or more amino acid sequences that occur in an amino acid translation of said one or more splice variants but not in the corresponding splice variant in the reference sample, and predicting HLA binding of the amino acid sequences in order to identify candidate shared antigen. The present invention also relates to methods of characterising and/or treating a medical condition, including cancer.

Provided herein are EMCN-specific antigen-binding domains, and chimeric proteins including the EMCN-specific antigen-binding. Also provided herein are cells, nucleic acids, vectors, compositions, and methods directed to proteins including the EMCN-specific antigen-binding domains.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a polyethylene glycol (PEG) receptors and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

A bi-specific genetically modified immune cell, comprising a first antigen binding moiety that is specific to CD83 and a second antigen binding moiety that is specific to interleukin 6 receptor (IL-6R). Also provided herein are uses of such bi-specific genetically modified immune cells for suppressing alloreactive donor cells in cell transplantation.

Provided is an engineered immune cell. The cell expresses a chimeric antigen receptor comprising an antigen-binding region. The antigen-binding region comprises an anti-CD7 antibody, and the expression of endogenous CD7, at least one TCR/CD3 gene, and at least one MHC-II related gene is suppressed or silenced. Further provided is the use of the engineered immune cell in the treatment of diseases associated with CD7 expression.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

The present disclosure provides transposon-based systems for introducing cellular therapeutic products, such as CAR and TCR, into a target immune cell. The transposon-based systems can carry larger payloads than conventional viral vector-based technologies, simplifying multi-genetic editing and can reduce undesired recombination between homologous sequences in the payload. Also provided is a shortened autologous process that can be completed within a few days, within one day or even within a few hours. Even without immune cell activation, enrichment or expansion, the resulting cell populations achieve greatly higher in vivo therapeutic efficacy than the much lengthier autologous process that employs viral vectors.

The invention relates to nucleic acid constructs comprising a combination of a first sequence encoding a CAR and second sequence encoding an amino acid transporter, and to cells comprising such nucleic acid constructs. It also relates to methods of manufacturing said cells, and to pharmaceutical compositions comprising said nucleic acid constructs or cells, for use in the treatment of diseases with cellular amino-acid depletion such as cancer.

The present invention relates to modified immune cells or precursors thereof, comprising dual (a first and a second) chimeric receptors (e.g. CARs). One aspect includes a first CAR comprising a 4-1BB intracellular domain and a second CAR comprising a CD28 intracellular domain. Another aspect includes a method for treating of an HIV infected mammal using a modified T cell comprising a first CD4 CAR comprising a 4-1BB intracellular domain and a second CD4 CAR comprising a CD28 intracellular domain.