Journal
JOURNAL OF IMMUNOLOGY
Volume 170, Issue 1, Pages 228-235Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.170.1.228
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Funding
- NATIONAL CANCER INSTITUTE [R01CA088956, T32CA071340] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI034824, R01AI031524] Funding Source: NIH RePORTER
- NCI NIH HHS [CA88956, T32 CA71340-05] Funding Source: Medline
- NIAID NIH HHS [AI34824, AI31524] Funding Source: Medline
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Tumor membrane Ag immobilized on cell size microspheres (large multivalent immunogen (LMI)) was previously shown to augment tumor-specific CTL activity and reduce tumor growth, and a clinical trial examining this approach is in progress. In the current study, LMI treatment has been examined using adoptive transfer of TCR-transgenic CD8 T cells to visualize Ag-specific cells during the response. OT-I T cells specific for H-2K(b)/OVA(257-264). were transferred into mice that were then challenged with LMI made by immobilizing H-2K(b)/OVA(257-264). on microspheres (K-b/OVA(257-264)-LMI) alone, or along with i.p. challenge with OVA-expressing E.G7 tumor. K-b/OVA(257-264)-LMI caused significant reduction of tumor growth when administered to E.G7-bearing mice. When administered alone, the K-b/OVA(257-264)-LMI caused only weak clonal expansion of OT-I cells in the spleen and lymph nodes, although most of the OT-I cells up-regulated expression of CD44 and VLA-4. In contrast, K-b/OVA(257-264)-LMI administration to E.G7-bearing mice stimulated no detectable expansion of OT-I cells in the spleen and lymph nodes but caused a rapid increase in the number of OT-I cells in the peritoneal cavity, the site of the growing tumor. These results demonstrate the potential for using class I/tumor peptide complexes for immunotherapy. In addition, they suggest a model for the mechanism of CTL augmentation in which recognition of the LMI Ag results in altered trafficking of the tumor-specific CD8 T cells so that they reach the site of a growing tumor more rapidly and in greater numbers, where they may further expand and acquire effector function.
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