Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Petkov, Stefan; Heuts, Frank; Krotova, Olga; Kilpeläinen, Athina; Engström, Gunnel; Starodubova, Elizaveta; Isaguliants, Maria

doi:10.4161/hv.25561

Cited by 25 publications

(31 citation statements)

References 30 publications

(36 reference statements)

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“…Resistance to tumor growth coincided with the induction of an IFN-γ response to CD8 T-cell epitope of luciferase represented by LucP peptide 21 , 22 , detectable after both prime and boost with Luc DNA (Fig. 9A ).…”

Section: Resultsmentioning

confidence: 96%

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Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer

Baklaushev

Kilpeläinen

Petkov

et al. 2017

Sci Rep

105

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Implantation of reporter-labeled tumor cells in an immunocompetent host involves a risk of their immune elimination. We have studied this effect in a mouse model of breast cancer after the orthotopic implantation of mammary gland adenocarcinoma 4T1 cells genetically labelled with luciferase (Luc). Mice were implanted with 4T1 cells and two derivative Luc-expressing clones 4T1luc2 and 4T1luc2D6 exhibiting equal in vitro growth rates. In vivo, the daughter 4T1luc2 clone exhibited nearly the same, and 4T1luc2D6, a lower growth rate than the parental cells. The metastatic potential of 4T1 variants was assessed by magnetic resonance, bioluminescent imaging, micro-computed tomography, and densitometry which detected 100-μm metastases in multiple organs and bones at the early stage of their development. After 3–4 weeks, 4T1 generated 11.4 ± 2.1, 4T1luc2D6, 4.5 ± 0.6; and 4T1luc2, <1 metastases per mouse, locations restricted to lungs and regional lymph nodes. Mice bearing Luc-expressing tumors developed IFN-γ response to the dominant CTL epitope of Luc. Induced by intradermal DNA-immunization, such response protected mice from the establishment of 4T1luc2-tumors. Our data show that natural or induced cellular response against the reporter restricts growth and metastatic activity of the reporter-labelled tumor cells. Such cells represent a powerful instrument for improving immunization technique for cancer vaccine applications.

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Section: Resultsmentioning

confidence: 96%

“…Plasmids were delivered by intradermal injections. Immediately after, mice were electroporated over the injection sites using DermaVax (Cellectis) generating driving pulses of 100 V (as described) 22 (n = 4) or CUY21 EditII (BEX Ltd.) generating driving pulses of 100 V (n = 6), or 50 V (n = 4).…”

Section: Resultsmentioning

confidence: 99%

Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer

Baklaushev

Kilpeläinen

Petkov

et al. 2017

Sci Rep

105

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“…Furthermore, it may be a concern that only 4T1 cells carried a luciferase reporter gene, which as a foreign gene could influence the differential tumor immunology between the 4T1-and Py230-based intraductal model. However, previous reports have shown that luciferase is a very weak antigen and does not significantly alter tumor progression (58,59). Moreover, 4T1 cells are also intrinsically weakly immunogenic and have a limited mutational burden (40,58).…”

Section: Discussionmentioning

confidence: 98%

Comparative Profiling of Metastatic 4T1- vs. Non-metastatic Py230-Based Mammary Tumors in an Intraductal Model for Triple-Negative Breast Cancer

et al. 2019

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“…Other studies have reported higher or equivalent antibody responses being generated in DNA vaccine studies after skin EP compared to muscle EP 3 , 25 , 41 , while others have reported lower levels. 42 , 43 The model antigen used in each these studies may account for these differences. Studies describing higher humoral responses after IM delivery used the weakly immunogenic Luciferase antigen whose expression level in the skin is 100th of that detected in the muscle.…”

Section: Discussionmentioning

confidence: 99%

DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response

Smith

Schultheis

Kiosses

et al. 2014

Molecular Therapy - Methods & Clinical Development

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The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response.

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Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Cited by 25 publications

References 30 publications

Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer

Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer

Comparative Profiling of Metastatic 4T1- vs. Non-metastatic Py230-Based Mammary Tumors in an Intraductal Model for Triple-Negative Breast Cancer

DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response

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