| First Author | Ly LV | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 21 | Pages | 8339-46 |
| PubMed ID | 20940397 | Mgi Jnum | J:165795 |
| Mgi Id | MGI:4838475 | Doi | 10.1158/0008-5472.CAN-10-2288 |
| Citation | Ly LV, et al. (2010) Peptide vaccination after T-cell transfer causes massive clonal expansion, tumor eradication, and manageable cytokine storm. Cancer Res 70(21):8339-46 |
| abstractText | Adoptive T-cell transfer (ACT) is successfully applied as a cancer treatment that is based on the activation and effector functions of tumor-specific T cells. Here, we present results from a mouse model in which ACT is combined with a long peptide-based vaccine comprising gp100 T-cell epitopes. Transferred CD8(+) T cells expanded up to 1,000-fold after peptide vaccination, leading to a 3-fold increase in white blood cell count and a very high frequency in the generation of antigen-specific memory T cells, the generation of which tended to correlate with effective antitumor responses. An enormous pool of effector T cells spread widely to different tissues, including the skin and the immune-privileged eye, where they mediate tumor eradication. Importantly, these striking T-cell dynamics occurred in immunocompetent mice without prior hematologic conditioning. Continued activation of the specific T-cell pool by vaccination led to strong T-cell-mediated cytokine storm and lethality due to multi-organ failure. However, this immunopathology could be prevented by controlling the rapid biodistribution of the peptide or by using a weakly agonistic peptide. Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts. |
