krn-7000 and Adenocarcinoma

The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site.. Patients with operable advanced lung cancer received an intravenous injection of α-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed.. Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs.. The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.

Topics: Adenocarcinoma; Aged; Antigen-Presenting Cells; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Galactosylceramides; Humans; Immunotherapy; Lung Neoplasms; Lymph Nodes; Male; Natural Killer T-Cells; Receptors, Antigen, T-Cell; Tumor Microenvironment

Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don't have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria

Topics: Adenocarcinoma; Animals; Bacteroides; Colonic Neoplasms; Galactosylceramides; Immunotherapy; Mice; Mice, Inbred C57BL; Natural Killer T-Cells; Prevotella

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cricetinae; Galactosylceramides; Liver Neoplasms; Pancreatic Neoplasms

Colorectal liver metastasis is clinically a major problem. We examined the antitumor activity of KRN7000, an alpha-galactosylceramide, on mice with liver metastases of adenocarcinoma Colon26 cells. KRN7000 treatment, beginning 1 day after tumor inoculation (day 1), significantly inhibited tumor growth in the liver, and its potency was equal to that of interleukin 12. KRN7000 treatment from day 3 caused regression of established Colon26 nodules. KRN7000 administration resulted in a high percentage of cured mice that acquired tumor-specific immunity. In addition, it appeared that highly activated, liver-associated natural killer cells made the major contribution to the killing of Colon26 cells in the liver. These results suggest that KRN7000 may be useful for the treatment of colorectal liver metastasis.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Animals; Antineoplastic Agents; Colorectal Neoplasms; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Female; Galactosylceramides; Interleukin-12; Killer Cells, Natural; Leukocytes, Mononuclear; Liver; Liver Neoplasms; Mice; Mice, Inbred BALB C; Neoplasms, Experimental