Combination immune therapy and cytokine control therapy for cancer treatment
Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, methods of treating a cancer or tumor, methods of reducing tumor load, methods of reducing the size or growth rate of a cancer or a tumor, and methods of extending of the survival of a subject suffering from a cancer or tumor, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. Compositions and methods of use thereof may increase the efficacy of a CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. In certain instances compositions may include additional chemotherapeutic or immunomodulatory agents.
1. A population of mononuclear apoptotic cells comprising mononuclear cells in an early-apoptotic state, wherein said population of mononuclear apoptotic cells is irradiated after production of said early apoptotic cells, wherein said irradiated mononuclear apoptotic cell population comprises:
(a) a decreased percent of non-quiescent non-apoptotic viable cells;
(b) a suppressed cellular activation of any living non-apoptotic cells; or
(c) a reduced proliferation of any living non-apoptotic cells;
or any combination thereof compared with a preparation comprising non-irradiated early apoptotic cell populations, wherein at least 50% of said cells are in an early apoptotic state and said early apoptotic population comprises less than 5% necrotic cells, and wherein the population of mononuclear apoptotic cells remains stable at said early-apoptotic state for about 48-72 hours.
2. The population of claim 1 , wherein the decreased percent of non-quiescent non-apoptotic viable cells is less than 10%.
3. The population of claim 1 , wherein said mononuclear apoptotic cell population comprises no viable non-apoptotic cells.
4. The population of claim 1 , wherein said mononuclear cell population is selected from the group consisting of: leukocytes, lymphocytes, monocytes, dendritic cells, and natural killer cells.
5. The population of claim 1 , wherein said irradiation comprises gamma irradiation or UV irradiation.
6. A pharmaceutical composition, comprising the population of claim 1 and a pharmaceutically acceptable excipient.