Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess t...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15037 |
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| author | Edoardo Agosti Marco Zeppieri Lucio De Maria Camilla Tedeschi Marco Maria Fontanella Pier Paolo Panciani Tamara Ius |
| author_facet | Edoardo Agosti Marco Zeppieri Lucio De Maria Camilla Tedeschi Marco Maria Fontanella Pier Paolo Panciani Tamara Ius |
| author_sort | Edoardo Agosti |
| collection | DOAJ |
| description | Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “glioblastomas,” “immunotherapies,” and “treatment.” The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability. |
| first_indexed | 2024-03-10T21:12:59Z |
| format | Article |
| id | doaj.art-a3290039dbfa47bf9038a6325d327779 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:12:59Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3290039dbfa47bf9038a6325d3277792023-11-19T16:40:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201503710.3390/ijms242015037Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for AdvancementsEdoardo Agosti0Marco Zeppieri1Lucio De Maria2Camilla Tedeschi3Marco Maria Fontanella4Pier Paolo Panciani5Tamara Ius6Department of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, ItalyDepartment of Ophthalmology, University Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, ItalyDepartment of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, ItalyNeurosurgery Unit, Head-Neck and NeuroScience Department, University Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, ItalyGlioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “glioblastomas,” “immunotherapies,” and “treatment.” The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.https://www.mdpi.com/1422-0067/24/20/15037glioblastomaimmunotherapytarget therapiesvaccinesmonoclonal antibodiesadoptive cell therapy |
| spellingShingle | Edoardo Agosti Marco Zeppieri Lucio De Maria Camilla Tedeschi Marco Maria Fontanella Pier Paolo Panciani Tamara Ius Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements International Journal of Molecular Sciences glioblastoma immunotherapy target therapies vaccines monoclonal antibodies adoptive cell therapy |
| title | Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements |
| title_full | Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements |
| title_fullStr | Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements |
| title_full_unstemmed | Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements |
| title_short | Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements |
| title_sort | glioblastoma immunotherapy a systematic review of the present strategies and prospects for advancements |
| topic | glioblastoma immunotherapy target therapies vaccines monoclonal antibodies adoptive cell therapy |
| url | https://www.mdpi.com/1422-0067/24/20/15037 |
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