Abstract: This application discloses microorganisms and methods of producing GNAQ/GNA11 inhibitors and methods of making antibody drug conjugates of anti-PMEL17 antibodies or antigen binding fragments conjugated to a GNAQ/GNA11 inhibitor. The disclosure also relates to formulations comprising antibody drug conjugates of anti-PMEL 17 antibodies or antigen binding fragments conjugated to a GNAQ/GNA1 inhibitor and methods of treating or preventing cancer using the formulations.

Abstract: Combination therapies comprising PD-1 inhibitors and other therapeutic agents used to treat or prevent cancerous conditions and disorders as follow. Combination therapies of three agents which are a PD-1 inhibitor, a CXCR2 inhibitor and a CSF-1/1R binding agent for treating a pancreatic cancer or a colorectal cancer. Combination therapies of three agents which are a PD-1 inhibitor, a CXCR2 inhibitor and an inhibitor of either TIM-3, C-MET or A2aR for treating a pancreatic cancer or a colorectal cancer. Combination therapies of three agents which are a PD-1 inhibitor, a LAG-3 inhibitor and (i) an inhibitor of either TGF-beta, TIM-3, C-MET, IL-1b or MEK or (ii) a GITR agonist or (iii) an A2aR antagonist or (iv) a CSF-1/1R binding agent for treating a breast cancer. Combination therapies of two agents which are a PD-1 inhibitor and a CXCR2 inhibitor for treating a pancreatic cancer, a colorectal cancer, a lung cancer or a breast cancer.

Abstract: A method of pulsing cultured hepatocytes, such as sandwich-cultured hepatocytes. The method includes providing a culture of hepatocytes, the culture having at least one bile canaliculus; exposing the culture of hepatocytes to a calcium-free buffer, whereby the contents of the at least one bile canaliculus are released; and removing the calcium-free buffer Pulsing cultured hepatocytes can reduce cholestasis arid can provide an in vitro culture of hepatocytes the more closely reflects in vivo hepatocyte characteristics.