The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

A group of chimeric antigen receptors (CARs) having two, three or four CAR molecules, wherein the members of the group of CARs can be different in their amino acid sequences, and wherein each of the CAR molecules of the group includes at least a transmembrane domain and an ectodomain comprising either an antigen binding moiety or a binding site to which another polypeptide is able to bind, wherein the polypeptide comprises an antigen binding moiety; wherein each CAR molecule of the group includes at least one dimerization domain, wherein this dimerization of a pair of dimerization domains is either induced by a regulating molecule and optionally reduced by another regulating molecule, or occurs in the absence of a regulating molecule and is reduced by a regulating molecule, and wherein the antigen binding moieties of the CAR molecules of the group specific for one target antigen.

Recombinant microorganisms, pharmaceutical compositions thereof, and methods of protein display on the cell surface of the microorganisms are disclosed.

Hematopoeitic stem/progenitor cells (HSPC) and/or non-T effector cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to activate, promote proliferation of, detect, enrich, isolate, track, deplete and/or eliminate modified cells. The cells can also be modified to express a binding domain.

The present invention relates to a recombinant virus of the family Paramyxoviridae comprising an expressible polynucleotide encoding at least one of (i) a tumor antigen, (ii) a fragment of a tumor antigen, and (iii) a variant of (i) or (ii). The present invention further relates to a polynucleotide encoding said recombinant virus of the family Paramyxoviridae and to a host cell comprising said recombinant virus of the family Paramyxoviridae and/or said polynucleotide encoding said recombinant virus of the family Paramyxoviridae. Moreover, the present invention relates to a method for activating immune cells with antitumor activity in a sample comprising cancer cells and to further means, methods, and uses related to the present invention.

An antitumor pharmaceutical combination includes (i) a compound ABX196 and (ii) at least one chemotherapeutic agent and/or at least one immunotherapeutic agent, for use in the treatment of cancer.

The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

The present invention includes compositions and methods that utilize a high affinity chimeric antigen receptor (CAR) with cross-reactivity to clinically-relevant EGFR mutated proteins.

Methods and compositions for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a targeted activated T cell, such as a bispecific antibody armed activated T cell (BAT), alone or in combination with an effective amount or a subtherapeutic amount of an additional therapeutic agent, wherein the targeted activated T cell selectively binds a cell of the cancer in the subject.

Methods and compositions for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a targeted activated T cell, such as a bispecific antibody armed activated T cell (BAT), alone or in combination with an effective amount or a subtherapeutic amount of an additional therapeutic agent, wherein the targeted activated T cell selectively binds a cell of the cancer in the subject.