Immunotherapy with MALP-2 suppresses pancreatic cancer in mice

Immunotherapy with macrophage activating lipopeptide 2 (MALP-2) induces tumor suppression in a mouse model of pancreatic carcinoma, according to a report in the March issue of Gut. The investigators will begin an early clinical trial of the strategy next month.

MALP-2 activates nuclear transcription factor kappaB, induces the synthesis of numerous cytokines and chemokines, induces maturation of dendritic cells, and induces in vitro tumoricidal activity of macrophages, the authors explain. Dr. Angela Maerten from University of Heidelberg, Germany and colleagues tested the tumor suppressive capacity of MALP-2 in a syngeneic pancreatic cancer mouse model. MALP-2 treatment significantly reduced subcutaneous tumor growth in mice and prolonged median survival from 18-19 days to 23 days, the authors report. In mice with established orthotopic tumors, MALP-2 treatment prolonged median survival from 16 days to 20 days with intraperitoneal treatment and from 19 days to 26 days with intratumoral injection. Treatment 9 days after tumor inoculation produced better results than did treatment 2 days after tumor inoculation, the researchers note, but weekly injections did not improve the results over single injections of MALP-2. The addition of MALP-2 to gemcitabine chemotherapy significantly prolonged median survival from 29 days to 37 days, the results indicate. Flow cytometric analysis demonstrated increases in cytotoxic T cells and natural killer (NK) cells, the investigators report, and histological studies showed progressive tumor cell necrosis with obvious infiltration of lymphocytes after MALP-2 treatment. “We will start to recruit patients for a phase I/II trial for patients with R2-resected pancreatic carcinoma in April at the Department of Surgery at the University of Heidelberg,” Dr. Maerten told Reuters Health. “Fifteen patients will receive an intratumoral injection of MALP-2 in the remaining tumor bed. We will start with 20?g MALP-2 and perform a dose-escalation. Two weeks after operation they will receive a standard chemotherapy (gemcitabine).” “A generalized activation of the immune system could break the tumor-induced immunosuppression and may lead, especially in multimodal regimens, to tumor control,” Dr. Maerten said. “I am sure that MALP-2 will act in the same way in other malignancies which might be sensitive against immunotherapeutics,” Dr. Maerten added. “Since it acts via an activation of the innate and the adaptive immune system, we do not expect limitations regarding MHC-deficient tumors.” (Source: Gut 2004;53:355-361: Reuters Health: Will Boggs, MD: March 2004: Oncolink)