| First Author | Hanada KI | Year | 2019 |
| Journal | JCI Insight | Volume | 4 |
| Issue | 10 | PubMed ID | 31092734 |
| Mgi Jnum | J:329644 | Mgi Id | MGI:6753691 |
| Doi | 10.1172/jci.insight.124405 | Citation | Hanada KI, et al. (2019) An effective mouse model for adoptive cancer immunotherapy targeting neoantigens. JCI Insight 4(10) |
| abstractText | The adoptive cell transfer (ACT) of T cells targeting mutated neoantigens can cause objective responses in varieties of metastatic cancers, but the development of new T cell-based treatments relies on accurate animal models. To investigate the therapeutic effect of targeting a neoantigen with ACT, we used T cells from pmel-1 T cell receptor-transgenic mice, known to recognize a WT peptide, gp100, and a mutated version of the peptide that has higher avidity. We gene-engineered B16 cells to express the WT or mutated gp100 epitopes and found that pmel-1-specific T cells targeting a neoantigen tumor target augmented recognition as measured by IFN-gamma production. Neoantigen expression by B16 also enhanced the capacity of pmel-1 T cells to trigger the complete and durable regression of large, established, vascularized tumor and required less lymphodepleting conditioning. Targeting neoantigen uncovered the possibility of using enforced expression of the IL-2Ralpha chain (CD25) in mutation-reactive CD8+ T cells to improve their antitumor functionality. These data reveal that targeting of "mutated-self" neoantigens may lead to improved efficacy and reduced toxicities of T cell-based cellular immunotherapies for patients with cancer. |
