222 Developing an adoptive cell transfer immunotherapy for pediatric high-grade gliomas

Frederico, Stephen C.; Sneiderman, Chaim; Pollack, Ian F.; Kohanbash, Gary

doi:10.1136/jitc-2022-sitc2022.0222

Cited by 3 publications

(2 citation statements)

References 1 publication

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“…Additionally, GBM patients are often immunosuppressed and are therefore not best positioned to fully respond to ICIs (79,80). Studies by Fecci and colleagues observed that patients with GBM have T-cell sequestration in the bone marrow due to the loss of the S1P1 receptor, while Giles and colleagues describe how dexamethasone (a corticosteroid commonly given to GBM patients to control cerebral edema) induces immunosuppression (18, 81).…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier

Frederico

Darling²,

Bielanin³

et al. 2023

Front. Immunol.

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Brain tumors are one of the leading causes of cancer related death in both the adult and pediatric patient population. Gliomas represent a cohort of brain tumors derived from glial cell lineages which include astrocytomas, oligodendrogliomas and glioblastomas (GBMs). These tumors are known to grow aggressively and have a high lethality with GBM being the most aggressive tumor in this group. Currently, few treatment options exist for GBM outside of surgical resection, radiation therapy and chemotherapy. While these measures have been shown to marginally improve patient survival, patients, especially those diagnosed with GBM, often experience a recurrence of their disease. Following disease recurrence, treatment options become more limited as additional surgical resections can pose life threatening risk to the patient, patients may be ineligible for additional radiation, and the recurrent tumor may be resistant to chemotherapy. Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy as many patients with cancers residing outside the central nervous system (CNS) have experienced a survival benefit from this treatment modality. It has often been observed that this survival benefit is increased following neoadjuvant administration of immune checkpoint inhibitors as tumor antigen is still present in the patient which enables a more robust anti-tumor immune response. Interestingly, results for ICI-based studies for patients with GBM have been largely disappointing which is a stark contrast from the success this treatment modality has had in non-central nervous system cancers. In this review, we will discuss the various benefits of neoadjuvant immune checkpoint inhibition such as how this approach reduces tumor burden and allows for a greater induction of an anti-tumor immune response. Additionally, we will discuss several non-CNS cancers where neoadjuvant immune checkpoint inhibition has been successful and discuss why we believe this approach may provide a survival benefit for GBM patients. We hope this manuscript will foster future studies aimed at exploring whether this approach may be beneficial for patients diagnosed with GBM.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier

Frederico

Darling²,

Bielanin³

et al. 2023

Front. Immunol.

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“…Brainstem tumors account for 10% of all pediatric tumors within the CNS with diffuse midline glioma (DMG) being the most common subtype. The prognosis for patients diagnosed with DMG is extremely poor as greater than 90% of patients die within 2 years of their initial diagnosis ( 2 , 3 ). Typical treatment of malignant gliomas involves surgical resection (in surgically accessible tumors), as well as chemotherapy and radiation therapy in lesions that are deemed higher risk ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Pre-clinical models for evaluating glioma targeted immunotherapies

Frederico

Zhang²,

Hu³

et al. 2023

Front. Immunol.

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Gliomas have an extremely poor prognosis in both adult and pediatric patient populations as these tumors are known to grow aggressively and respond poorly to standard of care treatment. Currently, treatment for gliomas involves surgical resection followed by chemoradiation therapy. However, some gliomas, such as diffuse midline glioma, have more limited treatment options such as radiotherapy alone. Even with these interventions, the prognosis for those diagnosed with a glioma remains poor. Immunotherapy is highly effective for some cancers and there is great interest in the development of effective immunotherapies for the treatment of gliomas. Clinical trials evaluating the efficacy of immunotherapies targeted to gliomas have largely failed to date, and we believe this is partially due to the poor choice in pre-clinical mouse models that are used to evaluate these immunotherapies. A key consideration in evaluating new immunotherapies is the selection of pre-clinical models that mimic the glioma-immune response in humans. Multiple pre-clinical options are currently available, each one with their own benefits and limitations. Informed selection of pre-clinical models for testing can facilitate translation of more promising immunotherapies in the clinical setting. In this review we plan to present glioma cell lines and mouse models, as well as alternatives to mouse models, that are available for pre-clinical glioma immunotherapy studies. We plan to discuss considerations of model selection that should be made for future studies as we hope this review can serve as a guide for investigators as they choose which model is best suited for their study.

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Myeloid cells as potential targets for immunotherapy in pediatric gliomas

Frederico,

Sharma,

Darling

et al. 2024

Front. Pediatr.

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Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive pediatric central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all pediatric CNS malignancies and has a 5-year survival rate of approximately 20%. Surgical resection and chemoradiation are often the standard of care for pGBM and pHGG, however, even with these interventions, survival for children diagnosed with pGBM and pHGG remains poor. Due to shortcomings associated with the standard of care, many efforts have been made to create novel immunotherapeutic approaches targeted to these malignancies. These efforts include the use of vaccines, cell-based therapies, and immune-checkpoint inhibitors. However, it is believed that in many pediatric glioma patients an immunosuppressive tumor microenvironment (TME) possess barriers that limit the efficacy of immune-based therapies. One of these barriers includes the presence of immunosuppressive myeloid cells. In this review we will discuss the various types of myeloid cells present in the glioma TME, including macrophages and microglia, myeloid-derived suppressor cells, and dendritic cells, as well as the specific mechanisms these cells can employ to enable immunosuppression. Finally, we will highlight therapeutic strategies targeted to these cells that are aimed at impeding myeloid-cell derived immunosuppression.

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222 Developing an adoptive cell transfer immunotherapy for pediatric high-grade gliomas

Cited by 3 publications

References 1 publication

Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier

Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier

Pre-clinical models for evaluating glioma targeted immunotherapies

Myeloid cells as potential targets for immunotherapy in pediatric gliomas

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