Modified integrin polypeptides are provided. Methods of identifying binding agents that bind to a modified integrin polypeptide are also provided.

The present disclosure relates to a novel-peptide-based anticancer immunotherapeutic agent, and to use, as an anticancer immunotherapeutic agent, of melittin, a variant thereof, analogues thereof, or a conjugate in which a drug is linked thereto. The melittin, the variant thereof or the analogues thereof, of the present disclosure, specifically bind to ITGB2, which is expressed on the cell membrane of M2 tumor-associated macrophages, so as to kill the M2 tumor-associated macrophages, and a conjugate in which a pro-apoptotic peptide or an anticancer drug is conjugated as a drug to the melittin, the variant thereof, or the analogues thereof remarkably increases apoptotic effects of the M2 tumor-associated macrophages, and thus can be used as an anticancer composition for suppressing tumor growth and metastasis.

The present invention is directed to transduced T cells expressing at least 100,000 molecules of human somatostatin receptor 2 (SSTR2), which improves PET/CT imaging sensitivity. The present invention is also directed to transduced T cells expressing SSTR2 and chimeric antigen receptor (CAR). In one embodiment, the CAR is specific to human ICAM-1 and the CAR comprises a binding domain that is scFv of anti-human ICAM-1, or an I domain of the L subunit of human lymphocyte function-associated antigen-1. In another embodiment, the CAR is specific to human CD19, and the CAR comprises a binding domain that is scFv of anti-human CD19. The present invention is further directed to using the above transduced T cells for monitoring T cell distribution in a patient by PET/CT imaging and/or treating cancer.

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the .sub.L subunit of human lymphocyte function-associated antigen 1 (LFA-1). The invention particularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 M Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells.

The present invention is directed to a genetically engineered cell and methods thereof as described herein.

Provided herein are modified NK-92 cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92 cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92 cells, as well as methods of treating cancer using the modified cells.

The instant disclosure provides multiple precision edits of bovine integrin beta 2 (CD18) that confer reduced susceptibility to Manheimia haemolytica leukotoxin A (LktA). Further disclosed are methods of producing genome-edited bovine cells, embryos, and animals comprising a modified CD18 incorporating the precision edits.