The present invention relates to modified T cell receptors (TCRs) and to their use in adoptive cell therapy (ACT), in particular for the transfer of T lymphocytes. The TCRs are mutated in the transmembrane regions of the alpha and beta chains with mutations favoring the correct TCR chain pairing. The correct pairing of the transferred exogenous alpha and beta TCR chains improves the functional activity and safety of the genetically modified T cells for the therapy of tumours and infectious diseases. The invention also relates to T cell receptor alpha or beta chain, to a recombinant TCR, a TCR complex, a nucleic acid coding for the TCR alpha or beta chain, to relative recombinant expression vector, host cells, pharmaceutical composition and to a method of detecting a hematological malignant cell, a solid tumor cell or an infected cell.

In certain embodiments, this disclosure relates to conjugates comprising a polypeptide of GM-CSF and a polypeptide IL-4. Typically, the GM-CSF and IL-4 are connected by a linker, e.g., polypeptide. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

Disclosed are biocompatible core/shell compositions suitable for the delivery of populations of mRNA molecules to mammalian cells. The disclosed core-shell structured multicomponent compositions are optimized for the delivery of mRNAs encoding one or more cancer- or tumor-specific antigens to a population of antigen presenting cells, including, for example, human dendritic cells, macrophages and B cells. Also disclosed are methods for use of these compositions as therapeutic cancer vaccines.

The present invention provides methods for isolating and cryopreserving tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, including methods via use of a kit and a semi-automatic device for aseptic disaggregation, enrichment, and cryopreservation of a resected tumor prior to expansion of the TIL population. The present invention also provides methods for expansion, and/or stabilization of TILs, for instance UTILs, compositions involving the same and methods of treatment involving the same.

The disclosure discloses a kind of new NKT-like cell subpopulation, a therapeutical composition comprising the NKT-like cell subpopulation, and the medical use thereof. The disclosure also provides a preparation method of the NKT-like cell subpopulation. The disclosed NKT-like cell subpopulation has a strong antitumor effect, and can be adoptive transferred into a subject to treat the tumor in the subject after in vitro cultured and amplified.

This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment.

In certain embodiments, this disclosure relates to conjugates comprising a polypeptide of GM-CSF and a polypeptide IL-4. Typically, the GM-CSF and IL-4 are connected by a linker, e.g., polypeptide. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

The subject matter described herein is directed to methods for determining the potency of isolated and expanded tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, and compositions involving the same and methods of treatment involving the same.

The present invention provides methods for expanding TILs and producing therapeutic populations of TILs. According to exemplary embodiments, at least a portion of the therapeutic population of TILs are gene-edited to enhance their therapeutic effect. According to further embodiments, methods for gene-editing TILs include intratumoral delivery of expression vectors for immune checkpoint inhibitors using an electroporation system prior to harvesting the tumor for TIL production. According to yet further embodiments, an adjuvant therapy for cancer includes delivery of expression vectors for immune checkpoint inhibitors before, after or before and after infusion of TILs for treating cancer.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill IL13Ra2-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with an IL13Ra2-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.