Stability Program in Dendritic Cell Vaccines: A “Real-World” Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center

Pancisi, Elena; Granato, Anna Maria; Scarpi, Emanuela; Ridolfi, Laura; Carloni, Silvia; Moretti, Cinzia; Giusti, Massimo; Rosa, Francesco De; Pignatta, Sara; Piccinini, Claudia; Soldati, Valentina; Calabrò, Luana; Framarini, Massimo; Stefanelli, Monica; Bulgarelli, Jenny; Tazzari, Marcella; Fanini, Francesca; Petrini, Massimiliano

doi:10.3390/vaccines10070999

Cited by 5 publications

(3 citation statements)

References 19 publications

(24 reference statements)

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“…Viability is one mandatory quality control of GMP-grade therapeutic DCs (39). In the present work we have found that although viability appears very high shortly after human cDC isolation, subsequent spontaneous apoptosis may be extensive following short-term culture.…”

Section: Discussionmentioning

confidence: 51%

GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2

et al. 2023

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Conventional type 1 dendritic cells (cDC1) and conventional type 2 dendritic cells (cDC2) have attracted increasing attention as alternatives to monocyte-derived dendritic cells (moDCs) in cancer immunotherapy. Use of cDCs for therapy has been hindered by their low numbers in peripheral blood. In the present study, we found that extensive spontaneous apoptosis and cDC death in culture within 24hrs represent an additional challenge. Different media conditions that maintain cDC viability and function were investigated. CD141+ cDC1 and CD1c+ cDC2 were isolated from healthy blood donor buffy coats. Low viabilities were found with CellGenix DC, RPMI-1640, and X-VIVO 15 standard culture media and with several supplements at 24hrs and 48hrs. Among multiple factors it was found that GM-CSF improved both cDC1 and cDC2 viability, whereas Flt3-L and IL-4 only increased viability of cDC1 and cDC2, respectively. Combinations of these three cytokines improved viability of both cDCs further, both at 24hrs and 48hrs time points. Although these cytokines have been extensively investigated for their role in myeloid cell differentiation, and are also used clinically, their effects on mature cDCs remain incompletely known, in particular effects on pro-inflammatory or tolerogenic cDC features. HLA-DR, CD80, CD83, CD86, PD-L1 and PD-L2 cDC membrane expressions were relatively little affected by GM-CSF, IL-4 and Flt3-L cytokine supplements compared to the strong induction following Toll-like receptor (TLR) stimulation for 24hrs. With minor exceptions the three cytokines appeared to be permissive to the TLR-induced marker expression. Allogeneic mixed leukocyte reaction showed that the cytokines promoted T-cell proliferation and revealed a potential to boost both Th1 and Th2 polarizing cytokines. GM-CSF and Flt3-L and their combination improved the capability of cDC1 for dextran uptake, while in cDC2, dextran capture was improved by GM-CSF. The data suggest that GM-CSF, IL-4 and Flt3-L and combinations might be beneficial for DC viability and function in vitro. Limited viability of cDCs could be a confounding variable experimentally and in immunotherapy.

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Section: Discussionmentioning

confidence: 51%

GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2

et al. 2023

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“…Another strategy involves utilizing autologous dendritic cells activated through exposure to tumor-associated antigens, along with enhancing the cellular response through exposure to adjuvant molecules (see Figure 2 ) [ 6 , 7 ]. Dendritic cells, serving as antigen-presenting cells, are inoculated autologously and activated, mirroring the approach seen with Sipuleucel-T, an approved therapy for metastatic prostate cancer [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Biofunctionalized Nanoparticles in Digestive Cancer Vaccine Development

Zdrehus,

Delcea,

Mocan

2024

Pharmaceutics

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Nanotechnology has provided an opportunity for unparalleled development of the treatment of various severe diseases. The unique properties of nanoparticles offer a promising strategy for enhancing antitumor immunity by enhancing immunogenicity and presentation of tumor autoantigens for cancer immunotherapy. Polymeric, liposomal, carbon or silica-based nanoparticles are among those with major immunomodulatory roles in various cancer treatments. Cancer vaccines, in particular digestive cancer vaccines, have been researched and developed on nanotechnological platforms. Due to their safety, controlled release, targeting of dendritic cells (DCs) and improved antigen uptake, as well as enhanced immunogenicity, nanoparticles have been used as carriers, as adjuvants for increased effect at the tumor level, for their immunomodulating effect, or for targeting the tumor microenvironment, thereby increasing tumor immunogenicity and reducing tumor inflammatory response. This review looks at digestive cancer vaccines developed on nanoparticle platforms and the impact nanoparticles have on the effects of these vaccines.

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“…It can regulate the innate and adaptive immune responses of patients through activating and resistance. These characteristics make them playing a central role in regulating the immune response and have been widely used in the clinical application of cancer [10]. Many researchers are committed to the exploration of DC cancer therapeutic vaccine, and many relevant reports have appeared as early as 1999 [11].…”

Section: Introductionmentioning

confidence: 99%

Development of cell-based vaccines in cancer treatment

Chen¹

2023

HSET

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Cancer, as a serious global disease, becomes a severe threat to human life. Due to the problems of environmental pollution and life habits, many people die each year from various kinds of cancer, which also includes many young and middle-aged people. Nowadays, cancer has become one of the most concerned public health problems in the world, and the efforts and attempts to actively explore new treatments for cancer have never stopped. The creation of therapeutic cancer vaccines has solid biological and preclinical rationales, however, it has been difficult to translate this treatment approach into the clinical therapies. Immunotherapy has gained widespread attention as an emerging tool for cancer treatment. Among them, cell-based vaccines have achieved ideal outcomes in multiple tumor killings. This review introduces vaccines based on induced pluripotent stem cells (iPSC) and dendritic cells (DC), summarizes the related research progress of cell vaccines in cancer treatment and discusses the limitations of cell-based vaccines.

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Stability Program in Dendritic Cell Vaccines: A “Real-World” Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center

Cited by 5 publications

References 19 publications

GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2

GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2

Role of Biofunctionalized Nanoparticles in Digestive Cancer Vaccine Development

Development of cell-based vaccines in cancer treatment

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