Individualized mRNA Neoantigen Vaccines provoke substantial T cell immunity in Pancreatic Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222011 | GEO | 2023/02/01
REPOSITORIES: GEO
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Project description:Individualized mRNA Neoantigen Vaccines provoke substantial T cell immunity in Pancreatic Cancer
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Project description:The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effect of cancer vaccines. Studies have shown that individualized and broad antigens can fully activate anti-tumor immunity and inhibiting the function of TGF-β can facilitate T cell migration to tumor sites. Based on our previous study, we introduced a new vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both individualized and broad antigens, to induce broad antitumor effects and cause immunogenic death. Encouraged by the proinflammatory effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the high affinity between TGF-βR2 and TGF-β, we developed RT-MPs with the SARS-CoV-2 spike protein and TGF-βR2. We found that this spike protein and high TGF-βR2 expression induces the innate immune response and ameliorates the immunosuppressive TME, thereby promoting T cell activation and infiltration, and ultimately inhibiting tumor growth. In addition, when combined with anti-programmed death 1 (anti-PD-1) the engineered RT-MPs were able to generate an immune memory response and eliminate subcutaneous tumors. Our study provides a novel strategy for producing an effective personalized anti-tumor vaccine for clinical application.
2023-10-27 | GSE239631 | GEO
Project description:The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effect of cancer vaccines. Studies have shown that individualized and broad antigens can fully activate anti-tumor immunity and inhibiting the function of TGF-β can facilitate T cell migration to tumor sites. Based on our previous study, we introduced a new vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both individualized and broad antigens, to induce broad antitumor effects and cause immunogenic death. Encouraged by the proinflammatory effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the high affinity between TGF-βR2 and TGF-β, we developed RT-MPs with the SARS-CoV-2 spike protein and TGF-βR2. We found that this spike protein and high TGF-βR2 expression induces the innate immune response and ameliorates the immunosuppressive TME, thereby promoting T cell activation and infiltration, and ultimately inhibiting tumor growth. In addition, when combined with anti-programmed death 1 (anti-PD-1) the engineered RT-MPs were able to generate an immune memory response and eliminate subcutaneous tumors. Our study provides a novel strategy for producing an effective personalized anti-tumor vaccine for clinical application.
2023-10-27 | GSE240108 | GEO
Project description:Individualized diagnosis prediction classifiers were successfully constructed through expression profiling of a total of 8,644 genes in 49 patients with relapse/refractory diffuse large B cell lymphoma, prospectively treated in a randomized trial. keyword(s): Diagnosis prediction
2011-09-29 | GSE26812 | GEO
Project description:The purpose of this study is 1) to evaluate the feasibility of manufacturing a patient-specific neoantigen cancer vaccine, which involves predicting the patient’s neoantigens and generating a vaccine that encodes the predicted neoantigens; and, 2) to identify and select patients who may be eligible for a shared neoantigen cancer vaccine where their tumor contains a specific shared mutation and who have the correct HLA allele capable of presenting the neoantigen derived from the tumor-specific mutation.
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Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 8,644 genes in 20 pancreatic cancer cases, which had been consecutively operated.
2024-11-02 | GSE246880 | GEO
Project description:Individualized diagnosis prediction classifiers were successfully constructed through expression profiling of a total of 8,644 genes in 49 patients with relapse/refractory diffuse large B cell lymphoma, prospectively treated in a randomized trial. keyword(s): Diagnosis prediction All lymphoma cases were predicted as belonging either to germical center B-cell like DLBCL or activated B cell like DLBCL based on the expression of a set of 54 genes (140 probes).
2011-09-28 | E-GEOD-26812 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.
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Project description:DNA mismatch repair deficiency (MMRD) drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. LS individuals are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a Phase I/IIa clinical trial. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not been demonstrated so far.
2021-08-30 | GSE175744 | GEO
Project description:The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC.
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