Provided herein, inter alia, nucleic acids including coding sequences for human CD80, IL-15, IL-15Rα polypeptides, wherein the coding sequence for hCD80 is operably positioned upstream to the coding sequences for hIL-15 and hIL-15Rα. The disclosure also provides recombinant cells, cell cultures, pharmaceutical compositions, and whole-cell vaccines containing the recombinant cells disclosed herein. Also disclosed are methods useful for treating myeloma and leukemias, such as acute myelogenous leukemia (AML).

Synthetic, biodegradable nanoparticles (NPs) encapsulating at least one of a signal 1 protein, a signal 2 protein, and/or a signal 3 protein are disclosed, which, when transfected into one or more a cancer cells, reprogram the one or more cancer cells into “tumor-derived APCs” in vivo to activate T-cells and natural killer (NK) cells for systemic tumor rejection. The NPs can be used for treating cancers, in particular metastatic cancers.

Tumor tissue, including soft and/or bony tissue, are harvested from a subject and morcellated. The morcellated tissue is placed in a cartridge which is placed in a containment chamber of a tumor tissue processing device. Cancer cells in the morcellated tumor tissue are destroyed without destroying tumor antigens therein. These cells are destroyed cryogenically by exposing the cartridge to a cooling fluid such as liquid nitrogen, optionally with a warming cycle, and optionally with more than one freezing/thawing cycle. The treated tissue and/or cells are then extracted from the cartridge and reintroduced to the subject after they have reached a threshold condition. The treated tissue and/or cells can be reintroduced via a containment sleeve or a reimplantation bag.

Anti-tumor immune response are generated by induction of activated B cells to provide costimulatory signals necessary for T cell activation. Certain compositions are combined with anti-immune checkpoint inhibitors to generate a synergistic anti-tumor response.

The present disclosure relates to protein molecules that specifically bind to 5T4 and/or 4-1BB. The molecules may have at least one humanized 5T4-binding or 4-1BB-binding domain. Such molecules are useful for the treatment of cancer. The protein molecule binding to 5T4 or 4-1BB may have a second binding domain that binds to another target. The molecules may bind both 5T4-expressing cells and a cell-surface molecule expressed by an effector cell to enhance effector cell activation, proliferation, survival and/or effector-cell mediated cytotoxicity. The disclosure also provides pharmaceutical compositions comprising the 5T4-binding or 4-1BB-binding polypeptide or protein molecules, nucleic acid molecules encoding these polypeptides and methods of making and using these molecules.

The present disclosure provides an allogeneic whole cell cancer vaccine platform that includes compositions and methods for treating and preventing breast cancer. Provided herein are compositions containing a therapeutically effective amount of cells from one or more cancer cell lines, some or all of which are modified to (i) inhibit or reduce expression of one or more immunosuppressive factors by the cells, and/or (ii) express or increase expression of one or more immunostimulatory factors by the cells, and/or (iii) express or increase expression of one or more tumor-associated antigens (TAAs), including TAAs that have been mutated, and which comprise cancer cell lines that natively express a heterogeneity of tumor associated antigens and/or neoantigens, and/or (iv) express one or more tumor fitness advantage mutations, including but not limited to driver mutations. Also provided herein are methods of making and preparing the breast cancer vaccine compositions and methods of use thereof.

In one aspect, the present invention provides a method for treating cancer comprising tumor cell vaccination in combination with hematopoietic and immune cell transplantation. In some embodiments, the method involves autologous tumor cell vaccination prior to autologous hematopoietic and immune cell transplantation. In another aspect, the present invention provides a method of purifying tumor cells from a subject in preparation for vaccination.

Chimeric antigen receptors containing CD33 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Described herein are methods and compositions for treating cancer. Various embodiments use engineered autologous or syngeneic cancer cells that home to tumors in vivo and deliver therapeutic polypeptides. Various embodiments further promote an anti-tumor immune response that can assist in treating existing tumors and provide protection against recurrent cancer.

The described invention provides allogeneic tumor cell vaccines comprising tumor cell lines or tumor cell line variants that are genetically engineered to express a core group of three immunomodulatory molecules, and optionally additional R immunomodulatory polypeptides for induction of one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and to then enter an effector phase for killing of tumor cells. According to some embodiments, the tumor cell vaccine candidate can induce an immune response in the recipient cancer patient that cross reacts with the patient's own (autologous) tumor cells, the effects of which are sufficient to result in enhanced anti-tumor immunity contributing to the increased survival of a vaccinated patient cohort compared to a matched unvaccinated patient cohort.