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| Home > Publications database > Long-peptide vaccination with driver gene mutations in p53 and Kras induces cancer mutation-specific effector as well as regulatory T cell responses. > print |
| Home > Publications database > Long-peptide vaccination with driver gene mutations in p53 and Kras induces cancer mutation-specific effector as well as regulatory T cell responses. > print |
| 001 | 142110 | ||
| 005 | 20240229105144.0 | ||
| 024 | 7 | _ | |a 10.1080/2162402X.2018.1500671 |2 doi |
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| 100 | 1 | _ | |a Quandt, Jasmin |0 P:(DE-HGF)0 |b 0 |e First author |
| 245 | _ | _ | |a Long-peptide vaccination with driver gene mutations in p53 and Kras induces cancer mutation-specific effector as well as regulatory T cell responses. |
| 260 | _ | _ | |a Abingdon |c 2018 |b Taylor & Franics |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1680693090_11715 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Mutated proteins arising from somatic mutations in tumors are promising targets for cancer immunotherapy. They represent true tumor-specific antigens (TSAs) as they are exclusively expressed in tumors, reduce the risk of autoimmunity and are more likely to overcome tolerance compared to wild-type (wt) sequences. Hence, we designed a panel of long peptides (LPs, 28-35 aa) comprising driver gene mutations in TP35 and KRAS frequently found in gastrointestinal tumors to test their combined immunotherapeutic potential. We found increased numbers of T cells responsive against respective mutated and wt peptides in colorectal cancer patients that carry the tested mutations in their tumors than patients with other mutations. Further, active immunization of HLA(-A2/DR1)-humanized mice with mixes of the same mutated LPs yielded simultaneous, polyvalent CD8+/CD4+ T cell responses against the majority of peptides. Peptide-specific T cells possessed a multifunctional cytokine profile with CD4+ T cells showing a TH1-like phenotype. Two mutated peptides (Kras[G12V], p53[R248W]) induced significantly higher T cell responses than corresponding wt sequences and comprised HLA-A2/DR1-restricted mutated epitopes. However, vaccination with the same highly immunogenic LPs strongly increased systemic regulatory T cells (Treg) numbers in a syngeneic sarcoma model over-expressing these mutated protein variants and resulted in accelerated tumor outgrowth. In contrast, tumor outgrowth was delayed when vaccination was directed against tumor-intrinsic Kras/Tp53 mutations of lower immunogenicity. Conclusively, we show that LP vaccination targeting multiple mutated TSAs elicits polyvalent, multifunctional, and mutation-specific effector T cells capable of targeting tumors. However, the success of this therapeutic approach can be hampered by vaccination-induced, TSA-specific Tregs. |
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| 700 | 1 | _ | |a Schlude, Christoph |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Bartoschek, Michael |0 0000-0002-1567-795X |b 2 |
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| 700 | 1 | _ | |a Cid-Arregui, Angel |0 P:(DE-He78)a30064f6b2d9ab959d35315d7668c091 |b 4 |u dkfz |
| 700 | 1 | _ | |a Schölch, Sebastian |0 0000-0003-0012-3177 |b 5 |
| 700 | 1 | _ | |a Reissfelder, Christoph |b 6 |
| 700 | 1 | _ | |a Weitz, Jürgen |b 7 |
| 700 | 1 | _ | |a Schneider, Martin |b 8 |
| 700 | 1 | _ | |a Wiemann, Stefan |0 P:(DE-He78)f6bebe05e7a748d3cbf9f59659567d52 |b 9 |u dkfz |
| 700 | 1 | _ | |a Momburg, Frank |0 P:(DE-He78)b2290261145f21c46f2d42783c69d104 |b 10 |u dkfz |
| 700 | 1 | _ | |a Beckhove, Philipp |0 P:(DE-He78)1732377f6242a18280bc6aaa196988d1 |b 11 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1080/2162402X.2018.1500671 |g Vol. 7, no. 12, p. e1500671 - |0 PERI:(DE-600)2645309-5 |n 12 |p e1500671 - |t OncoImmunology |v 7 |y 2018 |x 2162-402X |
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