Dataset Information

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines.

ABSTRACT: A promising personal immunotherapy is autologous dendritic cells (DC) loaded ex vivo with autologous tumor antigens (ATA) derived from self-renewing autologous cancer cells. DC-ATA are suspended in granulocyte-macrophage colony stimulating factor at the time of each subcutaneous injection. Previously, irradiated autologous tumor cell vaccines have produced encouraging results in 150 cancer patients, but the DC-ATA vaccine demonstrated superiority in single-arm and randomized trials in metastatic melanoma. DC-ATA have been injected into more than 200 patients with melanoma, glioblastoma, and ovarian, hepatocellular, and renal cell cancers. Key observations include: [1] greater than 95% success rates for tumor cell cultures and monocyte collection for dendritic cell production; [2] injections are well-tolerated; [3] the immune response is rapid and includes primarily TH1/TH17 cellular responses; [4] efficacy has been suggested by delayed but durable complete tumor regressions in patients with measurable disease, by progression-free survival in glioblastoma, and by overall survival in melanoma.

SUBMITTER: Dillman RO

PROVIDER: S-EPMC10294766 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines.

Dillman Robert O RO Nistor Gabriel I GI Keirstead Hans S HS

Human vaccines & immunotherapeutics 20230503 1

A promising personal immunotherapy is autologous dendritic cells (DC) loaded <i>ex vivo</i> with autologous tumor antigens (ATA) derived from self-renewing autologous cancer cells. DC-ATA are suspended in granulocyte-macrophage colony stimulating factor at the time of each subcutaneous injection. Previously, irradiated autologous tumor cell vaccines have produced encouraging results in 150 cancer patients, but the DC-ATA vaccine demonstrated superiority in single-arm and randomized trials in met ...[more]

PMID: 37133853

Similar Datasets

Project description:Abstract In primary glioblastoma (GBM), overall survival (OS) is poor despite standard aggressive therapy. Adjunctive AV-GBM-1 vaccine immunotherapy may improve OS. In this multi-institutional phase II trial, key eligibility criteria for intent-to-treat (ITT) enrollment were: (1) primary GBM, (2) age < 70 years when GBM was resected, (3) successful GBM cell culture, (4) successful monocyte collection by leukapheresis, (5) KPS > 70 post-surgery, and (6) plan to treat with concurrent RT/TMZ. Dendritic cells (DC) were differentiated from monocytes by culturing in IL-4 and granulocyte-macrophage colony stimulating factor (GM-CSF). AV-GBM-1 consisted of autologous DC incubated with autologous tumor antigens contained in the lysate of irradiated cultured GBM cells. After recovery from RT/TMZ, doses were admixed with 500 mcg GM-CSF; up to 8 doses were injected subcutaneously over 6 months. Patients were not excluded by apparent progression or pseudo-progression post RT/TMZ. OS and progression-free-survival (PFS) were calculated from ITT enrollment. The success rate was 97% for both GBM cell cultures and collection of monocytes; 60/60 vaccines were successfully manufactured. Median age was 59 years. 57 patients received 392 injections. After two weekly injections there were significant increases in plasma lipocalin-2 and angiopoietin-1, and decreases in thrombospondin-5, angiotensinogen, and beta-fibroblast growth factor. The most common adverse events attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). With follow up from 15.2 to 32 months, median PFS and OS were 10.3 (8.5,11.6 95% CI) and 16.0 (13.0,21.3 95% CI) months respectively. OS was better in the 25 patients who had methylguanine-methyltransferase (MGMT) methylation and/or isocitrate dehydrogenase (IDH) mutation. Age was not independently correlated with survival. From date of first injection, OS was not increased in 14 patients who were treated with alternating electrical tumor-treating fields. CONCLUSION: feasibility, safety, and PFS were encouraging. A phase III trial is in development. Clinicaltrials.gov NCT03400917.

Dataset Information

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines.

Publications

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets