Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model
The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/7/1254 |
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| author | Gábor J. Szebeni Róbert Alföldi Lajos I. Nagy Patrícia Neuperger Nikolett Gémes József Á. Balog László Tiszlavicz László G. Puskás |
| author_facet | Gábor J. Szebeni Róbert Alföldi Lajos I. Nagy Patrícia Neuperger Nikolett Gémes József Á. Balog László Tiszlavicz László G. Puskás |
| author_sort | Gábor J. Szebeni |
| collection | DOAJ |
| description | The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients. |
| first_indexed | 2024-03-11T00:34:46Z |
| format | Article |
| id | doaj.art-f75a057661764112b2285f31223e7e2d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T00:34:46Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-f75a057661764112b2285f31223e7e2d2023-11-18T21:41:47ZengMDPI AGVaccines2076-393X2023-07-01117125410.3390/vaccines11071254Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine ModelGábor J. Szebeni0Róbert Alföldi1Lajos I. Nagy2Patrícia Neuperger3Nikolett Gémes4József Á. Balog5László Tiszlavicz6László G. Puskás7Laboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, HungaryAstridBio Technologies Ltd., Wimmer Fülöp utca 1, H6728 Szeged, HungaryAvidin Ltd., Alsó Kikötő sor 11/D, H6726 Szeged, HungaryLaboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, HungaryLaboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, HungaryLaboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, HungaryDepartment of Pathology, University of Szeged, Állomás u. 2, H6725 Szeged, HungaryLaboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, HungaryThe advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients.https://www.mdpi.com/2076-393X/11/7/12544T1 triple-negative breast cancerwhole-cell vaccineUVC irradiationadoptive transfer |
| spellingShingle | Gábor J. Szebeni Róbert Alföldi Lajos I. Nagy Patrícia Neuperger Nikolett Gémes József Á. Balog László Tiszlavicz László G. Puskás Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model Vaccines 4T1 triple-negative breast cancer whole-cell vaccine UVC irradiation adoptive transfer |
| title | Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model |
| title_full | Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model |
| title_fullStr | Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model |
| title_full_unstemmed | Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model |
| title_short | Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model |
| title_sort | introduction of an ultraviolet c irradiated 4t1 murine breast cancer whole cell vaccine model |
| topic | 4T1 triple-negative breast cancer whole-cell vaccine UVC irradiation adoptive transfer |
| url | https://www.mdpi.com/2076-393X/11/7/1254 |
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