Cationic liposomes bearing IL-2 on their external surface induced mice leukocytes to kill human cervical cancer cells in vitro, and significantly reduced tumor burden in immunodepressed mice.
Tumor cells are known to modify their surroundings in order to escape immunologic detection, and IL-2, a killer cell activator, is one of the factors known to overcome this escape mechanism. In this regard, when we cocultured cells from the human cervical cancer cell line INBL with mice blood leukocytes, no inhibition of tumor cell growth was observed, but when a similar coculture was done in the presence of cationic liposomes bearing IL-2 on their external surface (CL-IL-2), all the INBL cells were killed. In order to evaluate whether this in vitro property of CL-IL-2 to overcome tumor cell detection by lymphocytes could also be reproduced in vivo, INBL cells were intraperitoneally (i.p.) inoculated into immunodepressed mice to produce solid tumors. We observed that the subsequent i.p. delivery of CL-IL-2 rendered the tumor masses significantly smaller. The presence of a large number of infiltrating lymphocytes on those tumors, and the fact that many had a cytotoxic CD8(+) phenotype suggests that these lymphocytes were responsible for the observed antitumor effect. Finally, the possible formation of a bridge between the IL-2R receptors on both, the lymphocytes and the INBL cells, mediated by the IL-2-bearing liposomes, and its possible effect on the activation of antitumor cytotoxic lymphocytes is discussed.
Rangel-Corona
Rosalva
R
Laboratorio de Oncología Celular, FES-Zaragoza, Universidad Nacional Autónoma de México, Mexico City, Mexico. raancor@yahoo.com.mx
Corona-Ortega
Teresa
T
del Río-Ortiz
Itzel
I
Nieves-Ramírez
Miriam E
ME
Morán-Bañuelos
Hirán
H
González-Tenorio
Olivia
O
Cáceres-Cortés
Julio Roberto
JR
Weiss-Steider
Benny
B
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology; D002412:Cations; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism*; D008081:Liposomes; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D015375:Receptors, Interleukin-2 / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D000970:Antineoplastic Agents; D002412:Cations; D007376:Interleukin-2; D008081:Liposomes; D015375:Receptors, Interleukin-2