Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them?
Glioblastoma (GBM) is an aggressive and fatal malignancy that despite decades of trials has limited therapeutic options. Antibody drug conjugates (ADCs) are composed of a monoclonal antibody which specifically recognizes a cellular surface antigen linked to a cytotoxic payload. ADCs have demonstrate...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.718590/full |
| _version_ | 1818571628177522688 |
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| author | Sagun Parakh Sagun Parakh Sagun Parakh Joseph Nicolazzo Andrew M Scott Andrew M Scott Andrew M Scott Andrew M Scott Hui Kong Gan Hui Kong Gan Hui Kong Gan Hui Kong Gan |
| author_facet | Sagun Parakh Sagun Parakh Sagun Parakh Joseph Nicolazzo Andrew M Scott Andrew M Scott Andrew M Scott Andrew M Scott Hui Kong Gan Hui Kong Gan Hui Kong Gan Hui Kong Gan |
| author_sort | Sagun Parakh |
| collection | DOAJ |
| description | Glioblastoma (GBM) is an aggressive and fatal malignancy that despite decades of trials has limited therapeutic options. Antibody drug conjugates (ADCs) are composed of a monoclonal antibody which specifically recognizes a cellular surface antigen linked to a cytotoxic payload. ADCs have demonstrated superior efficacy and/or reduced toxicity in a range of haematological and solid tumors resulting in nine ADCs receiving regulatory approval. ADCs have also been explored in patients with brain tumours but with limited success to date. While earlier generations ADCs in glioma patients have had limited success and high toxicity, newer and improved ADCs characterised by low immunogenicity and more effective payloads have shown promise in a range of tumour types. These newer ADCs have also been tested in glioma patients, however, with mixed results. Factors affecting the effectiveness of ADCs to target the CNS include the blood brain barrier which acts as a physical and biochemical barrier, the pro-cancerogenic and immunosuppressive tumor microenvironment and tumour characteristics like tumour volume and antigen expression. In this paper we review the data regarding the ongoing the development of ADCs in glioma patients as well as potential strategies to overcome these barriers to maximise their therapeutic potential. |
| first_indexed | 2024-12-14T13:58:33Z |
| format | Article |
| id | doaj.art-75bd5259ae494948a7493d5c5e2d644f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T13:58:33Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-75bd5259ae494948a7493d5c5e2d644f2022-12-21T22:58:47ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.718590718590Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them?Sagun Parakh0Sagun Parakh1Sagun Parakh2Joseph Nicolazzo3Andrew M Scott4Andrew M Scott5Andrew M Scott6Andrew M Scott7Hui Kong Gan8Hui Kong Gan9Hui Kong Gan10Hui Kong Gan11Department of Medical Oncology, Austin Hospital, Heidelberg, VIC, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, AustraliaSchool of Cancer Medicine, La Trobe University, Heidelberg, VIC, AustraliaDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, AustraliaSchool of Cancer Medicine, La Trobe University, Heidelberg, VIC, AustraliaDepartment of Medicine, University of Melbourne, Heidelberg, VIC, AustraliaDepartment of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, AustraliaDepartment of Medical Oncology, Austin Hospital, Heidelberg, VIC, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, AustraliaSchool of Cancer Medicine, La Trobe University, Heidelberg, VIC, AustraliaDepartment of Medicine, University of Melbourne, Heidelberg, VIC, AustraliaGlioblastoma (GBM) is an aggressive and fatal malignancy that despite decades of trials has limited therapeutic options. Antibody drug conjugates (ADCs) are composed of a monoclonal antibody which specifically recognizes a cellular surface antigen linked to a cytotoxic payload. ADCs have demonstrated superior efficacy and/or reduced toxicity in a range of haematological and solid tumors resulting in nine ADCs receiving regulatory approval. ADCs have also been explored in patients with brain tumours but with limited success to date. While earlier generations ADCs in glioma patients have had limited success and high toxicity, newer and improved ADCs characterised by low immunogenicity and more effective payloads have shown promise in a range of tumour types. These newer ADCs have also been tested in glioma patients, however, with mixed results. Factors affecting the effectiveness of ADCs to target the CNS include the blood brain barrier which acts as a physical and biochemical barrier, the pro-cancerogenic and immunosuppressive tumor microenvironment and tumour characteristics like tumour volume and antigen expression. In this paper we review the data regarding the ongoing the development of ADCs in glioma patients as well as potential strategies to overcome these barriers to maximise their therapeutic potential.https://www.frontiersin.org/articles/10.3389/fonc.2021.718590/fullantibody drug conjugates (ADC)gliomaglioblastomablood brain barriertumour microenvironmentbiomarkers |
| spellingShingle | Sagun Parakh Sagun Parakh Sagun Parakh Joseph Nicolazzo Andrew M Scott Andrew M Scott Andrew M Scott Andrew M Scott Hui Kong Gan Hui Kong Gan Hui Kong Gan Hui Kong Gan Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? Frontiers in Oncology antibody drug conjugates (ADC) glioma glioblastoma blood brain barrier tumour microenvironment biomarkers |
| title | Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? |
| title_full | Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? |
| title_fullStr | Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? |
| title_full_unstemmed | Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? |
| title_short | Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them? |
| title_sort | antibody drug conjugates in glioblastoma is there a future for them |
| topic | antibody drug conjugates (ADC) glioma glioblastoma blood brain barrier tumour microenvironment biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.718590/full |
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