The present invention relates to bispecific antibodies which bind to human carcinoembryonic antigen CEACAM5 (CEA) and human CD3ε. In addition, the present invention relates to polynucleotides encoding such bispecific antibodies and vectors and host cells comprising such polynucleotides. The invention further relates to methods for selecting and producing such antibodies and to methods of using such antibodies in the treatment of diseases.

The present invention relates to receptor tyrosine kinase-like orphan receptor 1 (ROR1) specific antigen binding molecules and associated fusion proteins and conjugates. In a further aspect, the present invention relates to conjugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

Herein is provided a recombinant tumor-selective viral particle comprising a nucleic acid encoding a recombinant polypeptide for directing an extracellular vesicle (EV) to at least one target cell, said recombinant polypeptide comprising: at least one targeting moiety for directing said EV to said at least one target molecule expressed by said at least one target cell; at least one EV-anchoring polypeptide; and at least one intravesicular polypeptide. The viral particle may be from an oncolytic viruses. Recombinant polypeptides for programming EVs to target particular molecules are also provided. Also described are therapeutic EVs for delivering payload polypeptides (and/or cargo molecules) to target cells, e.g., in vaccine or cell-free “CAR-T”-like applications, along with EVs for recruiting immune cells to target cells in EV-mediated BiTE -like applications. Oncolytic viruses may also be engineered to infect tumor cells and shed programmed EVs, yielding additional therapeutic effects.

The present application belongs to the technical field of immunotherapy, and specifically relates to a fusion protein for reversing a tumor microenvironment, a tumor immunosuppressive and resistant CAR and an expression vector, an immune cell and the use. The fusion protein is combined with different CAR structures of different targets, such as CEA, CD19, PSCA and BCMA, to form the tumor immunosuppressive and resistant CAR, or is used in combination with same to target and kill CD47 positive tumor cells; and the tumor immunosuppressive and resistant CAR and immune cells break through the influences of inhibitory signals on the function of CAR-T, which realizes the effectiveness of CAR-T treatment and can also ensure a certain degree of safety at the same time.

A method for refolding an antibody, a process for producing a refolded antibody, a refolded antibody, and uses thereof are provided. A method for refolding an antibody in a liquid phase comprises the steps of denaturing an inactive antibody binding directly or through a linker to a peptide, the peptide having an isoelectric point lower than the isoelectric point of the inactive antibody, and dispersing in a liquid phase the peptide-binding inactive antibody denatured in the step above. Also provided is a process for producing a refolded antibody.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.

Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein. In an embodiment, the splicing modulator comprises a pladienolide or a pladienolide derivative.

The invention provides an anti-CEA antibody for use in detecting CEA, treating disorders associated with CEA expression, diagnosing cancers characterized by aberrant CEA expression, and predicting effectiveness of cancer drug therapies.

Aspects of the present disclosure provide methods for treating a subject having a carcinoembryonic antigen (CEA)-positive tumor using a conditioning regimen (lymphodepleting treatment), which comprises administering one or more doses of a lymphodepleting agent to a subject, and a treatment regimen, which comprises administrating one or more doses of the anti-CEA CAR T cells and/or the ICK proteins to the subject.

The present invention generally relates to antigen binding receptors capable of specific binding to mutated Fc domains with reduced Fc receptor binding and T cells expressing these antigen binding receptors. More precisely, the present invention relates to T cells, transfected/transduced with an antigen binding receptor which is recruited by specifically binding to/interacting with the mutated Fc domain of therapeutic antibodies. Furthermore, the invention relates to a kit comprising the T cells of the invention and/or nucleic acid molecules, vectors expressing antigen binding receptors of the present invention and (a) tumor targeting antibody/antibodies comprising a mutated Fc domain. The invention also provides the production and use of T cells in a method for the treatment of particular diseases in conjunction with tumor-specific antibodies as well as pharmaceutical compositions/medicaments comprising T cells and/or therapeutic antibodies, wherein T cells are to be administered in combination with therapeutic-tumor targeting antibody/antibodies comprising a mutated Fc domain with reduced Fc receptor binding.