title: Immunomodulation in established murine tumors: response and survival rate enhancement by blood leukocyte-augmenting substance 236 (Cl-), a novel synthetic compound.
abstract: Immunomodulation in cancer has obvious appeal. Available data suggest the central role to be played by the host immune response in cancer outcome. Herein, we report a novel compound, Blood Leukocyte Augmenting Substance 236 (Cl(-)) [BLAS 236 (Cl(-))], which is able to restore and/or strengthen immunocompetence, which is critical in host-resistance to malignancy. The effects of several protocols in which BLAS 236 (Cl(-)) was given as single-agent or combined therapy on established murine tumors were evaluated in terms of long-term tumor-free survivors (>1 year). Treatment significantly improved overall complete response and survival rates and prolonged the life span of mice to beyond that of animals receiving placebo. The most outstanding protocols (denoted B3, B6 and D6, D7), were able to flatten tumor-free survival curves at the 80% and 100% levels, respectively (P < 0.001 for each protocol); these results compare favorably with those reported for other preclinical trials. Immunomodulation by BLAS 236 (Cl(-)) is viewed as a new efficient, safe way of potentiating and maintaining host-resistance to malignancy that holds promise as an adjuvant therapy alternative to current immune approaches for the ultimate cure of cancer.
authors.affiliation: Oncology Unit Community Autonomous of Madrid, Department of Immunopathology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Salomón
authors.initials: S
authors.lastname: Pérez Cuadrado
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Moreno Koch
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández Pérez
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Castejón Castán
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez Villalobos
authors.forename: María José
authors.initials: MJ
authors.lastname: González Mateos
authors.forename: Carlos Liñán
authors.initials: CL
authors.lastname: Olmos
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010919:Placebos; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; C488559:BLAS 236; D010919:Placebos; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; D003520:Cyclophosphamide; D011761:Pyrrolidonecarboxylic Acid