Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, the expansion employing a feeder cell population.

Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

Herein is reported an antibody binding to rabbit CD19 comprising (a) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 32 or 33 or 34, (b) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 35 or 36, (c) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37, (d) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38, (e) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39, and (f) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 40, as well as methods of using the same, especially in the identification and selection of antibody producing rabbit B-cells.

The present invention provides a porous hollow fiber membrane and methods of using the membrane to select an immune checkpoint inhibitor. The membrane can be used in animal models with an immune system and using low-cost common mouse. The host immune system is unable to attack the cancer cells within the membrane and animal study proves that the membrane system can be performed within animals.

Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.

Disclosed are means, methods, and compositions of matter useful for treatment of oncological indications through stimulation of protective anti-cancer immunity. In one embodiment the invention discloses the unexpected effect of astrocytes to augment immune stimulating activities of dendritic cells. In one embodiment dendritic cells are pulsed with tumor lysates and subsequently co-cultured with astrocytes in the presence of toll-like receptor agonists.

The present invention provides methods for isolating and cryopreserving tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, including methods via use of a kit and a semi-automatic device for aseptic disaggregation, enrichment, and cryopreservation of a resected tumor prior to expansion of the TIL population. The present invention also provides methods for expansion, and/or stabilization of TILs, for instance UTILs, compositions involving the same and methods of treatment involving the same.

Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

Provided are therapeutic agent including nucleic acid and CAR-modified immune cell and the use thereof. The therapeutic agent comprises first composition and second composition, the first composition comprises a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell; the labeling polypeptide has an extracellular antigen determining region, a spacer portion, and a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and/or cancer cell; the extracellular antigen determining region comprises one or more epitope polypeptides; wherein, amino acid sequences of proteins on cell membrane or secreted proteins of mammal do not comprise the epitope polypeptide amino acid sequence in the natural state; the second composition comprises chimeric antigen receptor modified immune cell which specifically recognize and bind to the extracellular antigen determining region. The therapeutic agent achieves synergistic therapeutic effect.

Provided herein are methods for treating metastasis of a cancer with a pharmaceutical composition comprising an effective amount of a cathepsin C (CTSC) inhibitor. The CTSC inhibitor, in some embodiments, is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for example, brensocatib. The treatment methods inhibit, slow, or reverse the progression of the metastasis. In some embodiments, the methods further comprise reducing neutrophil infiltration and/or formation of neutrophil extracellular traps (NETs).

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