The present invention relates to a CHO cell-derived protein secretory factor, an expression cassette in which a nucleic acid sequence encoding the protein secretory factor; and a gene encoding a target protein are operably linked, an expression vector comprising the expression cassette, a transformed cell into which the expression vector is introduced, and a method for producing a target protein using the transformed cell.

An exemplary combination drug includes (a1) an immunoresponsive cell expressing interleukine-7, CCL19, and a cell surface molecule that specifically recognizes a cancer antigen or (a2) one or more kinds of cells, one or more kinds of nucleic acid delivery vehicles, or a combination thereof, which cooperatively include a nucleic acid encoding interleukine-7 and a nucleic acid encoding CCL19; and (b) an immunosuppression inhibitor, and the drug is for use in treatment of a cancer in a subject. An exemplary immunoresponsive cell expresses interleukin-7, CCL19, an immunosuppression inhibiting polypeptide, and a cell surface molecule that specifically recognizes a cancer antigen.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

Provided herein are anaplastic lymphoma kinase chimeric antigen receptors (ALK CARs). The invention also provides polynucleotides encoding ALK CARs, engineered immune cells comprising an ALK CAR, pharmaceutical compositions thereof, and kits for administering the same. Methods of treating a subject with a disease by administering the ALK CAR or engineered immune cell comprising an ALK CAR, or pharmaceutical compositions thereof, are also provided.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

The present invention relates to an immunomodulator, and in particular to a chemokine-5 like agent with activities with a range of chemokine receptors. The invention relates to the use of this chemokine-like agent and variants thereof as a medicament.

A novel cytokine, U83A, is described, as are variant forms of the cytokine, having a wide range of agonistic and antagonistic activity against chemokine receptors. Uses of the chemokine in treatment of a range of diseases, including cancers and HIV/AIDS, are described.

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4.sup.+ T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4.sup.+ T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

The application provides non-viral vector, comprising an artificial immunosurveillance chimeric antigen receptor (AI-CAR) expression cassette flanked by two transposons or viral terminal repeats (IR), wherein the AI-CAR expression cassette comprises an inducible gene expression unit and a CAR expression unit.