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Atezolizumab plus personalized neoantigen vaccination in patients with urothelial cancer: a phase 1 trial

ABSTRACT: Atezolizumab plus personalized neoantigen vaccination in patients with urothelial cancer: a phase 1 trial

PROVIDER: PRJNA1222484 | ENA |

REPOSITORIES: ENA

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Atezolizumab plus personalized neoantigen vaccination in patients with urothelial cancer: a phase 1 trial

Project description:Atezolizumab plus personalized neoantigen vaccination in patients with urothelial cancer: a phase 1 trial

| PRJNA1222485 | ENA

A Study of a Personalized Neoantigen Cancer Vaccine

Project description:The purpose of this study is to evaluate the safety, dose, immunogenicity and early clinical activity of GRT-C901 and GRT-R902, a personalized neoantigen cancer vaccine, in combination with nivolumab and ipilimumab, in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer.

| 2281724 | ecrin-mdr-crc

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

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (NGS)

Project description:We designed a Phase II clinical trial testing the combination of guadecitabine (DNMTi) and atezolizumab (anti-PD-L1) with the goal to re-stimulate the immune mediated anticancer effects of immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma patients who were resistant to prior ICI treatment. No RECIST criteria responses were observed, however, patients could be separated into those with either progressive or stable disease outcomes. Analysis of the tumors did not show substantial DNA hypomethylation in the tumor or the upregulation of viral mimicry after two cycles of combination treatment. We did, however, observe that the therapy associated with immune activation of circulating immune cells and abundance of tumor-infiltrating CD8 T cells within the tumor, which were correlated with a longer survival outcome. Our results suggest that further studies to target the reprogramming of T cells with alternate methodologies may be of benefit in this disease setting.

2023-03-01 | GSE222932 | GEO

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (EPIC)

2023-03-01 | GSE222933 | GEO

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy

Project description:A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy

| PRJNA924046 | ENA

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (EPIC)

Project description:A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (EPIC)

| PRJNA924050 | ENA

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (NGS)

Project description:A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (NGS)

| PRJNA924049 | ENA

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