The present disclosure concerns combination therapy for cancer thatutilizes (i) an oncolytic virus; (ii) a virus comprising nucleic acid encoding an immunomodulatory factor; and (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen. In particular embodiments, the virus comprises nucleic acid encoding an immunomodulatory factor comprises nucleic acid encoding IL-12 and/or antagonist anti-PD-L1 antibody.

Provided herein are methods for preparing, producing, processing, culturing, isolating, or making cells suitable for immune or cell therapy, and for their use in cell therapy.

The present disclosure relates to methods and compositions to confer and/or increase immune responses mediated by cellular immunotherapy, such as by adoptively transferring tumor-specific genetically-modified subsets of lymphocytes. The disclosure provides compositions comprising genetically-modified lymphocytes that express at least two transgene(s) having the ability to modulate the immune system and the innate and adaptive immune response.

The present invention includes compositions and methods comprising viral vector systems for multiplexed activation of endogenous genes as immunotherapy and viral-based immune-gene therapy.

Checkpoint regulator antagonists that bind specifically to TIGIT, PD-1 and/or PD-L1 are disclosed. Also disclosed are methods of making and using the checkpoint regulator inhibitors, including monospecific, bispecific and trispecific checkpoint regulator antagonists thereof.

The present invention concerns a biomarker useful in adoptive cell therapy. The biomarker in question is CD150, otherwise termed SLAM or SLAMF1. Herein Applicants demonstrate that expression of CD150 on tumour infiltrating lymphocytes infusion products correlates with the response rate seen in those patients. High CD150 expression is found on patients who go on to have a complete response and low expression on patients who do not respond to therapy. The invention relates to the use of the biomarker to predict response rate or stratify patients for treatment. It also covers exploitation of this receptor in adoptive cell therapy regimens in general, including but not limited to over expression of the receptor in T-cell populations or isolation of cells expressing CD150 in an effort to increase efficacy.

The present invention relates to a nucleic acid molecule, a vector, a host cell, or a protein or peptide, or any combination thereof for use in a method of increasing efficiency of embryonic implantation in an in vitro fertilization programme, (I) wherein the at least one nucleic acid molecule is selected from nucleic acid molecules (a) encoding a polypeptide comprising or consisting of the amino acid sequence of any one of SEQ ID NOs 1 to 17, (b) comprising or consisting of the nucleotide sequence of any one of SEQ ID NOs 18 to 23, (c) encoding a polypeptide which is at least 85% identical, preferably at least 90% identical, and most preferred at least 95% identical to the amino acid sequence of (a), (d) consisting of a nucleotide sequence which is at least 95% identical, preferably at least 96% identical, and most preferred at least 98% identical to the nucleotide sequence of (b), (e) consisting of a nucleotide sequence which is degenerate with respect to the nucleic acid molecule of (d), (f) consisting of a fragment of the nucleic acid molecule of any one of (a) to (e), said fragment comprising at least 150 nucleotides, preferably at least 300 nucleotides, more preferably at least 450 nucleotides, and most preferably at least 600 nucleotides, and (g) corresponding to the nucleic acid molecule of any one of (a) to (f), wherein T is replaced by U, and (II) the vector comprises the nucleic acid molecule of (I); (III) the host cell is transformed, transduced or transfected with the vector of (II); and (IV) the at least one protein or peptide is selected from proteins or peptides being encoded by the nucleic acid molecule of (I); and wherein the method of increasing embryonic implantation efficiency comprises (i) contacting the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination thereof with the unfertilized, fertilized oocyte, and/or preimplantation embryo prior to the transfer of the fertilized oocyte or preimplantation embryo to the uterus; or (ii) contacting the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination thereof with the uterus prior to, simultaneously with and/or after the transfer of the fertilized oocyte or preimplantation embryo to the uterus; or (iii) systemically administering the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination prior to, simultaneously with and/or after the transfer of the fertilized oocyte or preimplantation embryo to the uterus, preferably via injection, transdermal and/or vaginal administration.

In one embodiment, a problem to be addressed by the present invention is to provide a novel cellular immunotherapy having a treatment and/or prevention effect against a tumor. In one embodiment, the present invention relates to a composition for use in treatment and/or prevention of a tumor in a subject comprising allogeneic CD4.sup.+ T cells, wherein the allogeneic CD4.sup.+ T cells have (a) MHC class II molecules all or part of which are different from MHC class II molecules of the subject, and contain (b) cells activated by ex vivo coculture with antigen-presenting cells derived from the subject or an individual having MHC class II molecules wholly identical or partially identical with the MHC class II molecules of the subject.

A method for treating a subject for glioblastoma is provided. In some embodiments, the method may comprise administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that, when bound to MOG, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of an immune cell therapy (e.g., a chimeric antigen receptor genetically modified T cell immunotherapy) and methods for manufacturing such immunotherapy. Some aspects of the disclosure relate to methods of determining objective response of a patient to an immune cell immunotherapy based on the levels of patient and product attributes prior to and after administration of the immunotherapy to the patient.