Combined chemokine and cytokine gene transfer enhances antitumor immunity.
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.
Dilloo
D
D
Division of Bone Marrow Transplantation, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Bacon
K
K
Holden
W
W
Zhong
W
W
Burdach
S
S
Zlotnik
A
A
Brenner
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019744:Chemokines, C; D002634:Chemotaxis, Leukocyte; D005260:Female; D005347:Fibroblasts / Q000637:transplantation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D019744:Chemokines, C; D007376:Interleukin-2; D008222:Lymphokines; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C486249:Xcl1 protein, mouse; C018997:lymphotactin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor