Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion-positive prostate cancer

Sanda, Martin G.; Dunn, Laura; Arredouani, Mohamed S.

doi:10.1007/s00262-013-1482-y

Cited by 14 publications

(12 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another gene that is being targeted 1215 for cancer therapy is ERG transcription factor, the gene 1216 with the most significant copy number gain in our anal-1217 ysis. Several studies have reported their attempts in de-1218 veloping drugs that target the ERG transcription fac-1219 tor, mostly in prostate cancer [244,245]. Further vali-1220 dation of the results described here would suggest the 1221 expansion of such trials to include melanoma.…”

mentioning

confidence: 78%

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

Mahas

Potluri

Kent

et al. 2016

CBM

View full text Add to dashboard Cite

Abstract. BACKGROUND: Skin melanocytes can give rise to benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. OBJECTIVE: This substantial difference between melanoma and benign nevi can be exploited to discriminate between melanoma and benign nevi. METHODS: Array-comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA copy number. In this study, high resolution, genome-wide single-nucleotide polymorphism (SNP) arrays were utilized to perform comprehensive and detailed analyses of recurrent copy number aberrations in 41 melanoma samples in comparison with 21 benign nevi. RESULTS: We found statistically significant copy number gains and losses within melanoma samples. Some of the identified aberrations are previously implicated in melanoma. Moreover, novel regions of copy number alterations were identified, revealing new candidate genes potentially involved in melanoma pathogenesis. CONCLUSIONS: Taken together, these findings can help improve melanoma diagnosis and introduce novel melanoma therapeutic targets.Keywords: Array comparative genomic hybridization, melanoma, FFPE highly lethal forms of cancer. Although it accounts 10 for the minority of skin cancers, a large majority 11 (75%) of skin cancer related-deaths are accounted for 12 by melanoma [1,2]. The incidence and mortality of 13 melanoma has increased dramatically in the last few 14 decades [3]. The American Cancer Society estimates 15 that about 73,870 people in United States will be diag-16 nosed with melanoma in 2015 and about 9,940 people 17 are expected to die from the disease. Importantly, the 18 5-year survival rate of melanoma depends on the stage 19 of the disease when it is diagnosed. It can be as high 20 as 98% when the melanoma is detected early before 21 it spreads to the lymph nodes or other organs. When 22 melanoma reaches the lymph nodes, the 5-year sur-23 vival rate drops to 62%, and to 15% when melanoma 24 spread to other organs [2]. Sequences for the primer pairs and cycling parame-286 ters were as follows: 5'-AATCGGGCTG-3' and 5'-287 GAAACGGGTG-3', 94• C for 2.5 minutes, then 45 cy-288 cles of 1 minute 94• C, 1 minute 55 • C and 2 minutes 289 72• C, then 7 minutes 72 • C and holding at 4 • C; or 5 -290 TGTGCCCAGTGAAGACTCAG-3' and 5 -GAGTGA 291 GCGGAGAGGGAACT-3', 45 cycles of 94• C for 1 292 minute, 35• C for 1 minute, and 72• C for 2 minute. 293 PCR products were resolved on 3% TBE agarose plus 294 SYBR Safe dye (Life Technologies). Gels were visu-295 alized with a GE ImageQuant LAS-3000 camera (GE 296 Healthcare Life Sciences, Piscataway, NJ, USA). Microarrays 298DNA copy number analysis was performed by hy-299 bridizing the extracted and qualified gDNA to Affy-300 metrix...

show abstract

mentioning

confidence: 78%

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

Mahas

Potluri

Kent

et al. 2016

CBM

View full text Add to dashboard Cite

show abstract

“…In our study, type VI fusions were present in 4 tumors (13%) and in each case led to predicted high-affinity fusion epitopes on autologous HLAs. Indeed, due to the prevalence of ERG alterations in prostate cancer, one study reported vaccine-induced immunity to ERG-derived HLA-A*02:01-restricted epitopes [48]. …”

Section: Discussionmentioning

confidence: 99%

Mutational Analysis of Gene Fusions Predicts Novel MHC Class I–Restricted T-Cell Epitopes and Immune Signatures in a Subset of Prostate Cancer

Kalina

Neilson

Lin

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose Gene fusions are frequently found in prostate cancer and may result in the formation of unique chimeric amino acid sequences (CASQs) that span the breakpoint of two fused gene products. This study evaluated the potential for fusion-derived CASQs to be a source of tumor neoepitopes, and determined their relationship to patterns of immune signatures in prostate cancer patients. Experimental Design A computational strategy was used to identify CASQs and their corresponding predicted MHC class I epitopes using RNA-Seq data from The Cancer Genome Atlas of prostate tumors. In vitro peptide-specific T cell expansion was performed to identify CASQ-reactive T cells. A multivariate analysis was used to relate patterns of in silico-predicted tumor-infiltrating immune cells with prostate tumors harboring these mutational events. Results Eighty-seven percent of tumors contained gene fusions with a mean of 12 per tumor. In total, 41% of fusion-positive tumors were found to encode CASQs. Within these tumors, 87% gave rise to predicted MHC class I-binding epitopes. This observation was more prominent when patients were stratified into low- and intermediate/high-risk categories. One of the identified CASQ from the recurrent TMPRSS2:ERG type VI fusion contained several high-affinity HLA-restricted epitopes. These peptides bound HLA-A*02:01 in vitro and were recognized by CD8+ T cells. Finally, the presence of fusions and CASQs were associated with expression of immune cell infiltration. Conclusions Mutanome analysis of gene fusion-derived CASQs can give rise to patient-specific predicted neoepitopes. Moreover, these fusions predicted patterns of immune-cell infiltration within a sub-group of prostate cancer patients.

show abstract

“…Since this discovery, many tumor antigens have been discovered that could be targeted by vaccines [15][16][17]. Based on these discoveries, several approaches using traditional antigen delivered in various adjuvants have been used to expand a population of tumor antigen specific T-cells.…”

Section: Using Vaccines To Treat Cancermentioning

confidence: 99%

The role of active vaccination in cancer immunotherapy: lessons from clinical trials

Sanda

2015

Current Opinion in Immunology

View full text Add to dashboard Cite

Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion-positive prostate cancer

Cited by 14 publications

References 38 publications

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

Mutational Analysis of Gene Fusions Predicts Novel MHC Class I–Restricted T-Cell Epitopes and Immune Signatures in a Subset of Prostate Cancer

The role of active vaccination in cancer immunotherapy: lessons from clinical trials

Contact Info

Product

Resources

About