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Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

ABSTRACT: Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

PROVIDER: PRJNA1129586 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29648066_1.fastq.gz	Fastqsanger.gz
	SRR29648066_2.fastq.gz	Fastqsanger.gz
	SRR29648067_1.fastq.gz	Fastqsanger.gz
	SRR29648067_2.fastq.gz	Fastqsanger.gz
	SRR29648068_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

Project description:Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficulty in identifying and screening neoantigen-specific T cells limits its widespread application. Here, we prepared neoantigen-reactive T cells (NRTs) after immunization with a tumor lysate-loaded dendritic cell (DC) vaccine (OCDC) for ACT. Our results demonstrated that the OCDC vaccine could induce a neoantigen-specific immune response, and it was feasible to prepare NRTs by loading immunogenic neoantigens onto DCs and coculturing them with spleen lymphocytes from mice immunized with the OCDC vaccine. We then transferred these NRTs back to the LL/2 tumor-bearing mice after OCDC vaccine immunization and found that OCDC vaccine and NRTs adoptive transfer combination treatment could induce a stronger antitumor response. Furthermore, we found that infused NRTs could migrate into the tumor microenvironment to exert antitumor effects. Our research provides a new and convenient method of preparing NRTs for ACT. The clinical translation of this approach has the potential to increase ACT efficacy.

2024-07-05 | GSE271086 | GEO

Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

2024-07-05 | GSE271085 | GEO

Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

Project description:Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

| PRJNA1129585 | ENA

Personalized neoantigen-based T cell therapy triggers cytotoxic lymphocytes expressing polyclonal TCR against metastatic ovarian cancer

Project description:Neoantigen-reactive cytotoxic T lymphocytes play a vital role in precise cancer cell elimination. In this study, we demonstrate the effectiveness of personalized neoantigen-based T cell therapy in inducing tumor regression in two patients suffering from heavily-burdened metastatic ovarian cancer. Our approach involved the development of a robust pipeline for ex vivo expansion of neoantigen-reactive T lymphocytes. Neoantigen peptides were designed and synthesized based on the somatic mutations of the tumors and their predicted HLA binding affinities. These peptides were then presented to T lymphocytes through co-culture with neoantigen-loaded dendritic cells for ex vivo expansion. Subsequent to cell therapy, both patients exhibited significant reductions in tumor marker levels and experienced substantial tumor regression. One patient achieved repeated cancer regression through infusions of T cell products generated from newly identified neoantigens. Transcriptomic analyses revealed a remarkable increase in neoantigen-reactive cytotoxic lymphocytes in the peripheral blood of the patients following cell therapy. These cytotoxic T lymphocytes expressed polyclonal T cell receptors (TCR) against neoantigens, along with abundant cytotoxic proteins and pro-inflammatory cytokines. The efficacy of neoantigen targeting was significantly associated with the immunogenicity and TCR polyclonality. Notably, the neoantigen-specific TCR clonotypes persisted in the peripheral blood after cell therapy. Our findings indicate that personalized neoantigen-based T cell therapy triggers cytotoxic lymphocytes expressing polyclonal TCR against ovarian cancer, suggesting its promising potential in cancer immunotherapy.

2023-12-01 | GSE248401 | GEO

Mutational and neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

Project description:Purpose: Utility of immunological treatment in cancer has increased; however, many patients do not respond to treatment. Identification of robust predictive biomarkers is required to correctly stratify patients. Although clinical trials based on adoptive T cell therapy (ACT) have yielded high response rates and many durable responses in melanoma, 50-60% of the patients have no clinical benefit. Herein, we searched for predictive biomarkers to ACT in melanoma. Methods: Whole exome- and transcriptome sequencing, neoantigen prediction and immune cell signature analysis were applied to pre-treatment melanoma samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously been treated with other immunotherapies. Results: We found that clinical benefit was associated with significantly higher neoantigen load (P=0.025). High mutation and neoantigen load were significantly associated with improved progression-free and overall survival (P=8x10^-4 and P=0.001, respectively). Further, gene-expression analysis of pre-treatment biopsies showed that clinical benefit was associated with strong immune activation signatures including a high MHC-I antigen processing and presentation score. Conclusions: These results improve our understanding of clinical benefit of ACT in melanoma, which can lead to clinically useful predictive biomarkers to be used for selecting patients that benefit from these highly intensive treatment regimens.

2017-12-04 | GSE100797 | GEO

Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

Project description:Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

| PRJNA429518 | ENA

Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

Project description:Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

| PRJNA429519 | ENA

Personalized neoantigen peptide vaccine for advanced solid cancer

Project description:Interventions: Personalized neoantigen peptide vaccine consists of 15-30 long peptides combined into four distinct immunizing peptide pools with 0.3 mg of each peptide admixed with 0.5 mg poly-ICLC per pool in a volume of 1 ml.;Experimental Biological/Vaccine;Personalized Neoantigen Peptide vaccine Primary outcome(s): Overall response rate at week 9, 18 on treatment period and every 12 weeks until disease progression or up to 12 months modified RECIST 1.1

| 2568253 | ecrin-mdr-crc

CD4 T cell activating neoantigens enhance personalized cancer vaccine efficacy

Project description:Personalized cancer vaccines aim to activate and expand cytotoxic anti-tumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy. To determine the effects of neoantigen-specific CD4+ T cell activation, we generated a new vaccine (PancVAX2) targeting both MHCI- and MHCII-specific neoantigens. Tumor-bearing mice vaccinated with PancVAX2 had significantly improved control of tumor growth and long-term survival benefit without concurrent administration of checkpoint inhibitors. PancVAX2 significantly enhanced priming and recruitment of neoantigen-specific CD8+ T into the tumor with lower PD1 expression after reactivation compared to the CD8+ vaccine alone. Vaccine-induced neoantigen- specific Th1 CD4+ T cells in the tumor were associated with decreased T regulatory cells (Tregs). Consistent with this, PancVAX2 was associated with more pro-immune myeloid-derived suppressor cells and M1-like macrophages in the tumor demonstrating a less immunosuppressive tumor microenvironment. This study demonstrates the biological importance of prioritizing and including CD4 T cell-specific neoantigens for personalized cancer vaccine modalities.

2023-12-11 | GSE244992 | GEO

NeoDisc: A neoantigen discovery pipeline for the development of personalized cancer immunotherapy

Project description:The accurate identification and prioritization of antigenic peptides presented by class-I and -II human leukocyte antigens (HLA-I and -II) recognized by autologous T cells is crucial for the development of cancer immunotherapies. While several clinical neoantigen prediction pipelines are now publicly available, none of them allows the direct integration of mass spectrometry immunopeptidomics data that can uncover antigenic peptides derived from various canonical and non-canonical sources. Therefore, we have developed and shared a unique ‘end-to-end’ clinical proteo-genomic pipeline, called NeoDisc. NeoDisc is a fast and modular computational pipeline that combines state-of-the-art publicly available and in-house software for genomics, transcriptomics, mass-spectrometry-based immunopeptidomics, and in silico tools for the identification, prediction, and prioritization of tumor-specific and immunogenic antigens from multiple sources. We demonstrated the application of NeoDisc for personalized antigen discovery, in the context of heterogenic antigenic landscape and defective cellular antigen presentation machineries, and we highlighted its clinical implementation.

2024-08-30 | PXD047641 | Pride

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