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 leukoc...

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Bibliographic Details
Published in:Journal of drug targeting 2011-02, Vol.19 (2), p.79-85
Main Authors: Rangel-Corona, Rosalva, Corona-Ortega, Teresa, del Río-Ortiz, Itzel, Nieves-Ramírez, Miriam E., Morán-Bañuelos, Hirán, González-Tenorio, Olivia, Cáceres-Cortés, Julio Roberto, Weiss-Steider, Benny
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - immunology
Cations
Cell Line, Tumor
Coculture Techniques
Disease Models, Animal
Drug Delivery Systems
Female
Humans
IL-2 liposomes
Immunocompromised Host
Interleukin-2 - administration & dosage
Interleukin-2 - immunology
Leukocytes - metabolism
Liposomes
Lymphocytes, Tumor-Infiltrating - immunology
Mice
Mice, Inbred CBA
Receptors, Interleukin-2 - immunology
Targeted drug delivery
tumor regression
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - immunology
Uterine Cervical Neoplasms - pathology
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Summary: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.
ISSN:1061-186X
1029-2330
DOI:10.3109/10611861003733920