Abstract B118: Manufacturing patient-specific autologous dendritic cell vaccines targeting antigens from autologous tumor cells that were self-renewing in liquid cell culture and injecting such vaccines to treat patients with advanced cancer
Authors: Dillman Robert O. , Nistor Gabriel I. , Keirstead Hans S. 
Published: February 2025

Background: After traditional vaccination, the first step in vivo is antigen processing by antigen-presenting cells, such as dendritic cells (DCs); therefore, DC vaccines consisting of autologous DC already loaded with antigens ex vivo may be more effective than injecting antigens. Autologous tumor antigens (ATA) may be preferable to shared tumor-associated antigens because of their cancer specificity and the uniqueness of personal neoantigens resulting from non-synonymous mutations. Targeting ATA expressed by cancer stem cells and early progenitor cells may be preferable to targeting antigens only expressed by terminally differentiated tumor cells. For these reasons, we have produced and tested autologous DC-ATA vaccines using short-term cultures of self-renewing cells as the ATA source. Methods: Surgically resected tumor tissue is processed into cell suspension, then cultured in liquid media that favors stem cell and progenitor cell proliferation. Irradiated tumor cells (ITC) or lysates of ITC serve as ATA sources. Peripheral blood mononuclear cells are collected by leukapheresis and enriched for monocytes (MC) by ficoll density centrifugation or elutriation lateral flow separation. Immature DC are differentiated from fresh or cryopreserved MC by culturing with granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-4. Antigen loading is accomplished by incubating DC with either ITC or ITC lysate. At weeks 1, 2, 3, 8, 12, 16, 20, and 24 cryopreserved DC-ATA doses are thawed, suspended in 500 mcg GM-CSF, and injected subcutaneously. Clinical trials have been conducted in melanoma, glioblastoma (GBM), and renal cell, hepatocellular, and ovary cancers. Results: Before 2014 the success rate for establishing tumor cell lines was only about 50% in melanoma and renal cell cancer and much lower for other cancers. Subsequently, using proprietary stem cell media has resulted in success for 183/188 patients (97.3%). Leukapheresis provided sufficient monocyte numbers for 235/240 patients (97.9%). 201 patients have received at least one DC-ATA injection; none discontinued DC-ATA because of adverse events (AE), most of which were brief, self-limited, mild to moderate local injection site reactions or flu-like symptoms. In randomized trials, there was no difference in the grade or frequency of AEs for DC-ATA vs ITC in melanoma nor for DC-ATA vs MC in ovary cancer, but there were more favorable immune responses for DC-ATA vs ITC and DC-ATA vs MC. Ten percent of patients with measurable metastatic lesions (3/30) had delayed, durable, complete remissions but there were no objective responses per RECIST during treatment. In GBM PFS was 50% longer than for historical controls. In melanoma, OS was longer compared to historical controls treated with ITC, and longer compared to ITC in a randomized trial. Conclusions: This DC-ATA approach is feasible in all tumor types that have been tested. Further investigation is warranted based on the lack of significant toxicity and the suggestion of efficacy.

Citation Format: Robert O. Dillman, Gabriel I. Nistor, Hans S. Keirstead. Manufacturing patient-specific autologous dendritic cell vaccines targeting antigens from autologous tumor cells that were self-renewing in liquid cell culture and injecting such vaccines to treat patients with advanced cancer [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B118.