ライフサイエンスコーパス: neoantigen

1 e generating tumor-specific mutant peptides (neoantigens).

2 gnizable immunogenic peptides, also known as neoantigens.

3 leukocyte antigens or depletion of expressed neoantigens.

4 ses against tumor-associated antigens and/or neoantigens.

5 n and the display of potentially immunogenic neoantigens.

6 ral defence genes and potentially expressing neoantigens.

7 ng novel protein sequences and a plethora of neoantigens.

8 ng, or copy-number loss of previously clonal neoantigens.

9 proach for inducing T cell immunity to tumor neoantigens.

10 an additional, unrecognized source of tumor neoantigens.

11 pertoire of somatic mutations and associated neoantigens.

12 lective pressure against gene fusion-derived neoantigens.

13 quencing the patient's tumor DNA to discover neoantigens.

14 nabling more sensitive discovery of putative neoantigens.

15 improving algorithms to predict immunogenic neoantigens.

16 ence of an adaptive immune response to these neoantigens.

17 pplied to targeting other tumors with public neoantigens.

18 ing lymphocytes (TILs) that recognize cancer neoantigens.

19 us single-nucleotide variants (SNVs), or SNV neoantigens.

20 hemotherapy by leveraging responses to tumor neoantigens.

21 fusions in prostate cancers that may produce neoantigens.

22 s and immunotherapeutic approaches targeting neoantigens.

23 as compared with non-synonymous SNV derived neoantigens.

24 finity recognizing distinct conformations of neoantigens.

25 g is an effective platform to uncover tumour neoantigens.

26 ly applied to identify mutations and predict neoantigens.

27 of identified variant peptides and putative neoantigens.

28 ated antigens, oncofetal antigens and shared neoantigens.

29 h the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise fr

30 he TIL infusion and recognized two KRAS-G12D neoantigens, a nonamer and a decamer, all restricted by

31 SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in nonhuman primate

32 s often the major criterion for prioritizing neoantigens, although little progress has been made towa

33 ive to immunotherapy because of dMMR-induced neoantigens and activation of the cGAS-STING pathway.

34 dentification of patient-specific mutations, neoantigens and biomarkers, and facilitated by advances

35 T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing

36 which can trigger an increased abundance of neoantigens and greater mutant-binding specificity.

37 clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epito

38 insights demonstrating the interplay between neoantigens and the immune system in untreated non-small

39 This source of neoantigens and the method to discover them may be usefu

40 The identification of immunogenic neoantigens and their cognate T cells represents the mos

41 as a contiguous means of predicting putative neoantigens and their corresponding recognition potentia

42 rlapping with that of MHC class I-restricted neoantigens and therefore needs to be considered when id

43 f potential signaling and metabolic targets, neoantigens, and biomarkers.

44 f potential signaling and metabolic targets, neoantigens, and biomarkers.

45 patients do not express, or express too few, neoantigens, and hence are less responsive to immune the

46 ation of naturally processed ligands, cancer neoantigens, and T cell epitopes.

47 technological advances utilized to identify neoantigens, and the T cells that recognize them, in ind

48 lockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncog

49 Furthermore, recognition of neoantigens appears an important driver of the clinical

50 d cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modality; h

51 Importantly, these properties of neoantigens are also predictive in human datasets, sugge

52 predicts that, without immune escape, tumor neoantigens are either clonal or at low frequency; hyper

53 Furthermore, predicted neoantigens are identified and associated with character

54 However, only a small fraction of predicted neoantigens are immunogenic.

55 The sequence of these FS neoantigens are predictable, allowing creation of a pept

56 s have demonstrated that T cells recognizing neoantigens are present in most cancers and offer a spec

57 Although the majority of cancer neoantigens are unique to each patient, and therefore no

58 IgE-mediated reactions towards these neoantigens are well studied; however, IgE-independent r

59 Neoantigens arise from mutations in cancer cells and are

60 ce suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main m

61 e patient's immune response to their tumor's neoantigens arising from DNA mutations.

62 he main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins.

63 ion of minor histocompatibility antigens and neoantigens arising from personal somatic alterations or

64 Neoantigens arising from these mutations are distinctly

65 R and MPL mutations provide a rich source of neoantigens as a result of their unique ability to bind

66 ons and reduced expression of genes encoding neoantigens as potential mediators of resistance to immu

67 implicate immunological ignorance of clonal neoantigens as the basis for ineffective T cell immunity

68 peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetan

69 In addition to identifying candidate neoantigens associated with fusions, we were able to use

70 ess by mutations, abundant mutations release neoantigens, attracting anti-cancer immune cells.

71 of the major obstacles to using personalized neoantigen-based cancer immunotherapy.

72 ally tailor neoantigens could facilitate the neoantigen-based translational immunotherapy research.TR

73 In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors

74 l, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with

75 lterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies fro

76 sic immunology, rational vaccine design, and neoantigen binding prediction for cancer immunotherapy.

77 eoantigenic peptide sequence and also affect neoantigen binding predictions.

78 alter the peptide sequence and may influence neoantigen binding.

79 Neoantigen burden is a major determinant of tumor immuno

80 Finally, high neoantigen burden was positively associated with genes r

81 associated with increased tumor mutation and neoantigen burden, which in turn were linked with greate

82 troma was observed in tumors with low clonal neoantigen burden.

83 earchers, and clinicians alike, on predicted neoantigen burdens while providing high-level insights i

84 as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings.

85 nalized cancer immunotherapies use predicted neoantigens, but most neoantigen prediction strategies d

86 In conclusion, enhanced immunity due to neoantigens can be one of possible forces to counterbala

87 We hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-spec

88 ever, to accurately prioritize the potential neoantigen candidates according to their ability of acti

89 chanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and

90 uch as nanoparticle vaccines customized with neoantigens, cell therapies based on patient-derived den

91 andscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immu

92 CRalphabeta heterodimers specific for clonal neoantigens confirmed correct TCR clonotype assignments

93 ting these strategies to individually tailor neoantigens could facilitate the neoantigen-based transl

94 roaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic a

95 on pressure, but the extent of the resulting neoantigen depletion remains unclear.

96 Apparent neoantigen depletion signals become negligible when taki

97 cellular immunotherapy targeting a "public" neoantigen derived from nucleophosmin 1 (NPM1), which is

98 Furthermore, neoantigens derived from indel mutations were nine times

99 ches to cancer have taken advantage of tumor neoantigens derived from somatic mutations.

100 Genomics-based neoantigen discovery can be enhanced by proteomic eviden

101 the integration of widely adopted tools for neoantigen discovery NeoPredPipe offers a contiguous mea

102 monstrate the application of our gene fusion neoantigen discovery pipeline, called INTEGRATE-Neo, by

103 , we extended this approach for personalized neoantigen discovery.

104 ly infiltrated tumours exhibited a waning of neoantigen editing during tumour evolution, indicative o

105 es shows direct evidence of fs-indel derived neoantigens eliciting immune response, particularly thos

106 dissect the immune response to personalized neoantigens encoded by tumor-specific mutations.

107 l responses against dominant and subdominant neoantigen epitopes derived from mutations, and leads to

108 Vs) encoding putative HLA class I-restricted neoantigen epitopes.

109 ncer by constructing a mathematical model of neoantigen evolution.

110 ent lymphocytes can mount a response against neoantigens expressed in microsatellite-stable gastroint

111 In neoantigen-expressing tumors, NK cell stimulation enhanc

112 As expected, neoantigen expression during lung adenocarcinoma develop

113 Neoantigen expression in OS was lacking and significantl

114 By contrast, neoantigen expression in pancreatic ductal adenocarcinom

115 , which demonstrate immunoediting, decreased neoantigen expression, and tumor-specific immune toleran

116 JA to create tumor cell lines with inducible neoantigen expression, which could be used to study anti

117 CR clonotypes were identified despite clonal neoantigen expression.

118 can impact immunosurveillance by modulating neoantigen expression.

119 event leakiness and allow tight control over neoantigen expression.

120 od and tumors was restricted to a few clonal neoantigens featuring an oligo-/monoclonal T cell-recept

121 In neoantigen-fixed models, dMLH1 tumors potently induce T

122 This BNP can capture cancer neoantigens following RT, enhance their uptake in dendri

123 ggesting that they can be used to prioritize neoantigens for individualized neoantigen-specific immun

124 endogenous tumour antigens, such as TAAs and neoantigens, for treating B cell malignancies.

125 requirement for direct, drug-induced stress, neoantigen formation, and stimulation of an innate respo

126 dictions are corroborated by the analysis of neoantigen frequencies and immune escape in exome and RN

127 However computing capabilities to identify neoantigens from genomic sequencing data are a limiting

128 kflow for identifying patient-specific tumor neoantigens from next generation sequencing data.

129 nsitively and accurately predict immunogenic neoantigens from next-generation sequencing data.

130 throughput means of predicting and assessing neoantigens from tumor variants that may stimulate immun

131 of a peptide array representing all possible neoantigen FS peptides.

132 Targeting cancer neoantigens generated by tumor-exclusive somatic mutatio

133 Moreover, neoantigen generation (through posttranslational modific

134 ating fusions and demonstrate that targeting neoantigens has clinical relevance even in low-mutationa

135 indings suggest that MHC class II-restricted neoantigens have a key function in the anti-tumour respo

136 , and autoreactive T cells that target these neoantigens have been identified.

137 the immunopositive and immunonegative MHC-I neoantigens have distinct spatial distribution patterns

138 There is growing evidence that tumour neoantigens have important roles in generating spontaneo

139 ipe is able to rapidly provide insights into neoantigen heterogeneity, burden, and immune stimulation

140 The focus of indel-derived neoantigen identification has been on leveraging DNA seq

141 applications such as vaccine design, cancer neoantigen identification, development of diagnostics an

142 urrent study provided feasible pipelines for neoantigen identification.

143 Two different pipelines of neoantigens identification were established in this stud

144 Importantly, low-fitness neoantigens identified by our method may be leveraged fo

145 dentify CD8+ or CD4+ lymphocytes recognizing neoantigens identified by whole-exome sequencing in 7 pa

146 clones on metastatic progression, suggesting neoantigen immunoediting.

147 tic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on

148 ch may provide key information for inferring neoantigens' immunogenicity.

149 described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs.

150 ibrary and used NetMHC to predict 149 unique neoantigens in 62% of MPN patients.

151 w negative selection shapes the clonality of neoantigens in a growing cancer by constructing a mathem

152 ure use of adoptive T cell therapy targeting neoantigens in bladder cancer.

153 egies that can be employed to exploit cancer neoantigens in clinical interventions.

154 e existence of circulating T cells targeting neoantigens in GI cancer patients and provide an approac

155 Here we discover neoantigens in human mantle-cell lymphomas by using an i

156 Increased neoantigens in hypermutated cancers with DNA mismatch re

157 ll reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer,

158 Inducible expression of neoantigens in mice would enable the study of endogenous

159 pothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make th

160 ive source to identify lymphocytes targeting neoantigens in patients with GI cancer with relatively l

161 Despite the presence of numerous neoantigens in patients, complete tumour elimination is

162 le studies of how T cells respond to defined neoantigens in the context of peripheral tolerance, tran

163 thods considers the original DNA loci of the neoantigens in the perspective of 3D genome which may pr

164 its fitness as a weighted effect of dominant neoantigens in the subclones of the tumour.

165 en qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as C

166 immunotherapy, DENDRO delineates the role of neoantigens in treatment response.

167 iew the evidence for the relevance of cancer neoantigens in tumor control and the biological properti

168 ns create highly immunogenic frameshift (FS) neoantigens in tumors.

169 Neoantigens induced by random mutations and specific to

170 ic T(H)17 responses are responsible for this neoantigen-induced tumor progression in PDAC.

171 t endogenous CD8 and CD4 T cell responses on neoantigen induction in peripheral tissues.

172 ncer cells via the DNA damage signalling and neoantigen-interferon-gamma pathway under oxidative stre

173 Our data indicate that the CBFB-MYH11 fusion neoantigen is naturally presented on AML blasts and enab

174 ever, timely and efficient identification of neoantigens is still one of the major obstacles to using

175 umoral heterogeneity (ITH) and the resultant neoantigen landscape on T cell immunity are poorly under

176 provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticl

177 c markers (such as tumor mutation burden and neoantigen load) and the degree of CD8(+) T cell infiltr

178 f clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or

179 lting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell t

180 mes of all cancers and therefore have a high neoantigen load.

181 Subsequently, neoantigen-loaded dendritic cell vaccines and neoantigen

182 ologous recombination deficiency, increasing neoantigen loads (all p < 0.01).

183 expansion of T cell clones in the setting of neoantigen loss.

184 ctor T cell responses directed toward cancer neoantigens mediate tumor regression following checkpoin

185 and the false negative rate (strong-binding neoantigens missed) across peptides of lengths 8-11 were

186 reactive microbial epitopes, consistent with neoantigen molecular mimicry.

187 nation of mice with SNP-7/8a using predicted neoantigens (n = 179) from three tumor models induced CD

188 Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoa

189 Here we develop inversion-induced joined neoantigen (NINJA), using RNA splicing, DNA recombinatio

190 In addition, epitope spread to neoantigens not included in the vaccine was detected pos

191 Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune respon

192 In tumors with neoantigen or MHC-I loss, T(EX) instead utilize IFNG to

193 l reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than ca

194 gh intratumor heterogeneity (ITH) for cancer neoantigens paradoxically attenuates anti-tumor immune r

195 (2) An inventory-shared neoantigen peptide library of common solid tumors was co

196 and in 6 of 13 patients who performed shared neoantigen peptide library, respectively.

197 ients' hotspot mutations were matched to the neoantigen peptide library.

198 f-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist

199 for major histocompatibility complex class I neoantigen peptides, the overall false discovery rate (i

200 romising cancer treatment modality; however, neoantigen physicochemical variability can present chall

201 nation against prototypic mutation-generated neoantigens, potentiated the antitumor effect of PD-1 an

202 Finally, we demonstrated that indel neoantigens predicted from RNA-seq were associated with

203 the overall false discovery rate (incorrect neoantigens predicted) and the false negative rate (stro

204 Here, validated, defined neoantigens, predicted neoepitopes, and mutations of dri

205 Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our

206 Here we offer NeoPredPipe (Neoantigen Prediction Pipeline) as a contiguous means of

207 herapies use predicted neoantigens, but most neoantigen prediction strategies do not consider proxima

208 vides a new perspective toward more accurate neoantigen prediction which eventually contribute to per

209 within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct

210 ational burden (TMB) as surrogate marker for neoantigens presented.

211 Although a few neoantigen prioritization methods have been proposed to

212 DNN-GFS demonstrated increased neoantigen prioritization power comparing to existing se

213 amed NeoFlow to support proteogenomics-based neoantigen prioritization, enabling more sensitive disco

214 etwork model (DNN-GFS) that is optimized for neoantigen prioritization.

215 ion show high microsatellite instability and neoantigen production.

216 ered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neo

217 Investigating the specific neoantigen qualities promoting T-cell activation in long

218 More broadly, we identify neoantigen quality as a biomarker for immunogenic tumour

219 immunogenicity model significantly improves neoantigen ranking.

220 Moreover, neoantigen-reactive T cells and a T cell receptor (TCR)

221 eoantigen-loaded dendritic cell vaccines and neoantigen-reactive T cells were generated for personali

222 f cancer, no study to date has shown whether neoantigen-reactive TILs can be found in bladder tumors.

223 Although previous studies have identified neoantigen-reactive TILs from several types of cancer, n

224 This finding suggests that neoantigen-reactive TILs reside in bladder cancer, which

225 Most antitumor neoantigen-reactive TILs were found in the differentiate

226 a high-efficiency method for inducing tumor neoantigen release in situ, which has great potential fo

227 ersonalized identification and validation of neoantigens remains a major challenge.

228 3B1-mutated patients may offer an unexplored neoantigen repertoire in MPNs.

229 CD8+ and CD4+ lymphocytes targeting 6 and 4 neoantigens, respectively.

230 While neoantigens result from the hypermutable nature of dMMR,

231 "cold" tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumo

232 FSPs are tumor-specific neoantigens shared across patients with MSI.

233 "off-the-shelf" cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tu

234 Unlike the patient-specific nature of SNV neoantigens, some alternative TSAs may have the advantag

235 D-L2 and that PD-L2 overexpression inhibited neoantigen specific T cell IFN-gamma production.

236 lastoma-generated circulating polyfunctional neoantigen-specific CD4(+) and CD8(+) T cell responses t

237 De novo neoantigen-specific CD4(+) and CD8(+) T cell responses w

238 Although the role of tumour neoantigen-specific CD8(+) T cells in tumour rejection i

239 and dose alter the magnitude and quality of neoantigen-specific CD8(+) T cells.

240 red to increase the breadth and diversity of neoantigen-specific CD8+ T cells.

241 -substituted (AAS) peptides revealed diverse neoantigen-specific CD8+ T responses, each composed of m

242 ic colon cancer patients, we detected CD8(+) neoantigen-specific cells targeting the mutated SMAD5 an

243 and significantly inhibit the progression of neoantigen-specific colorectal tumors.

244 licited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even

245 Here we show that durable neoantigen-specific immunity is regulated by mRNA N(6)-m

246 to prioritize neoantigens for individualized neoantigen-specific immunotherapies.

247 enerate enriched populations of personalized neoantigen-specific lymphocytes and isolate TCRs that co

248 tinal (GI) cancers, and adoptive transfer of neoantigen-specific lymphocytes has demonstrated antitum

249 We found that neoantigen-specific lymphocytes were preferentially enri

250 protocol designed for the detection of rare neoantigen-specific memory T cells in cancer patients fo

251 gen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8(+) T cells than CpG,

252 ient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to

253 ed oncolytic virus is able to activate tumor neoantigen-specific T cell responses, providing a potent

254 results provide insights into the nature of neoantigen-specific T cells and the effects of checkpoin

255 receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood ca

256 ith neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broa

257 arious tumors of the 4 patients examined, no neoantigen-specific TCR clonotypes were identified despi

258 the cognate neoepitope for a subject-derived neoantigen-specific TCR.

259 ponders retained a pool of CD39(-) stem-like neoantigen-specific TILs that was lacking in ACT nonresp

260 have typically been based upon personalized neoantigen-specific vaccines; however, in this issue of

261 s) permitted functional validation regarding neoantigen specificity.

262 types, while preserving tumor-reactivity and neoantigen-specificity shared with circulating immune ce

263 Across independent cancer neoantigen studies, peptides with high MARIA scores are

264 s inhibitors, chemoradiation, complexes with neoantigen-targeted monoclonal antibodies, combinations

265 omise, progress and challenges for improving neoantigen-targeted T cell-based immunotherapies for can

266 Neoantigen-targeted therapies have typically been based

267 Neoantigen-targeting vaccines thus have the potential to

268 We used personalized neoantigen-targeting vaccines to immunize patients newly

269 ly leukemia specific, making them attractive neoantigen targets for immunotherapy.

270 Rapid identification of immunostimulatory neoantigen targets hastens neoantigen vaccine developmen

271 are presented on AML and that CLAVEEVSL is a neoantigen that can be efficiently targeted on AML by De

272 e fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic

273 tions that result in several cancer-specific neoantigens that activate T-cells indicating that they a

274 sed immune system frequently responds to the neoantigens that arise as a consequence of this DNA dama

275 or-expressed 'neoepitopes' actually generate neoantigens that can be functionally recognized and prov

276 us offering a rapid way to screen for cancer neoantigens that can be targeted by subsequent T cell-ba

277 hat gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy.

278 PTEN loss and had reduced expression of two neoantigens that demonstrated strong immunoreactivity wi

279 Tumor-specific mutations can generate neoantigens that drive CD8 T cell responses against canc

280 ions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses.

281 for tumours based on immune interactions of neoantigens that predicts response to immunotherapy.

282 These mtDNA mutations encode neoantigens that provoke an immune response that is high

283 Targeting 'neoantigens'-the somatic mutations expressed only by tum

284 Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss m

285 ssess the ability to form novel antigens, or neoantigens, through haptenation of proteins and can sti

286 not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control

287 geted 58 (60%) and 15 (16%) of the 97 unique neoantigens used across patients, respectively.

288 rategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested

289 immunostimulatory neoantigen targets hastens neoantigen vaccine development.

290 of a phase 1B study in which a personalized neoantigen vaccine was combined with programmed death re

291 ncludes immune checkpoint blockade, personal neoantigen vaccines, and adoptive T cell transfer.

292 ive therapeutic strategies, including cancer neoantigen vaccines.

293 showed that the presence of mutant-specific neoantigens was associated with upregulation of antigen

294 ression-associated mutations whose predicted neoantigens were highly correlated with infiltration of

295 Neoantigens, which are derived from tumour-specific prot

296 related with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides

297 lized vaccines targeting dormancy-associated neoantigens, which can be given to patients with early s

298 these alterations, including the presence of neoantigens, which serve as potential immunotherapeutic

299 r models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity a

300 Major challenges to targeting neoantigens with T cells include heterogeneity and varia