Nature Medicine
2, 1090 - 1095 (1996)
doi:10.1038/nm1096-1090
Combined chemokine and cytokine gene transfer enhances antitumor immunityDagmar Dilloo1, Kevin Bacon2, William Holden1, Wanyun Zhong1, Stefan Burdach3, Albert Zlotnik2
& Malcolm Brenner1, 2
1Division of Bone Marrow Transplantation and Cell and Gene Therapy Program, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA
2DNAX Research Institute, 901 California Avenue, Palo Alto, California 94304-1104, USA
3Laboratory of Experimental Hematology, Heinrich Heine University, Moorenstrasse 5, D-40225 Duesseldorf, Germany
4Correspondence should be addressed to M.B. The probability of producing a specific antitumor response should be increased by multiplying the number of T lymphocytes that encounter the malignant cells. We tested this prediction in a murine model, using a recently discovered T−cell chemokine, lymphotactin (Lptn). This chemokine increased tumor cell infiltration with CD4+ lymphocytes but generated little antitumor activity. Coexpression of the T−cell growth factor interleukin−2, however, greatly expanded the T lymphocytes attracted by Lptn, affording protection from the growth of established tumor in a CD4+ and CD8+ T cell−dependent manner. Lesser synergy was seen with GM−CSF. Hence coexpression of a T−cell chemokine and T−cell growth factor potentiates antitumor responses in vivo, suggesting a general strategy to improve cancer immunotherapy.
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