Faculty Opinions recommendation of Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas.

✓ Surgical specimens from six benign and 16 malignant human gliomas were investigated immunohistochemically to correlate the degree of malignancy, the distribution of transforming growth factor-alpha (TGF-α) and epidermal growth factor (EGF) receptor, and the potential for cell proliferation using monoclonal antibodies to TGF-α, EGF receptor, and Ki-67. Fourteen (88%) of the malignant gliomas and one (17%) of the benign gliomas were found to be positive for TGF-α, and 14 (88%) of the malignant gliomas and two (33%) of the benign gliomas expressed EGF receptor. The proliferation index with Ki-67 was 18.8% ± 8.1% (mean ± standard deviation) in malignant gliomas and 1.9% ± 1.8% in benign gliomas. In general, cells positive for EGF receptor and Ki-67 were randomly distributed throughout the tumor tissue, and cells positive for TGF-α tended to be clustered without obvious relationship to areas of necrosis or blood vessels. In some tumors, cells positive for TGF-α, EGF receptor, and Ki-67 were associated in a focal distribution. The more frequent expression of TGF-α and EGF receptor in the highly proliferative malignant gliomas is compatible with a role for TGF-α and EGF receptor in the induction or stimulation of malignant gliomas.

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Immunotherapy for recurrent glioblastoma: practical insights and challenging prospects

Cell Death and Disease ◽

10.1038/s41419-021-03568-0 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Xin Wang ◽

Jie Lu ◽

Gaochao Guo ◽

Jinming Yu

Keyword(s):

T Cell ◽

Cell Therapy ◽

Cell Function ◽

Recurrent Glioblastoma ◽

Peptide Vaccination ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Specific Peptide

AbstractGlioblastoma (GB) is the most common high-grade intracranial malignant tumor with highly malignant biological behavior and a high recurrence rate. Although anti-PD-1/PD-L1 antibodies have achieved significant survival benefits in several kinds of solid tumors, the phase III clinical trial Checkmate 143 demonstrated that nivolumab, which targets PD-1, did not achieve survival benefits compared with bevacizumab in recurrent glioblastoma (rGB) patients. Nevertheless, neoadjuvant anti-PD-1 therapy followed by surgery and adjuvant anti-PD-1 therapy could effectively activate local and systemic immune responses and significantly improve the OS of rGB patients. Furthermore, several studies have also confirmed the progress made in applying tumor-specific peptide vaccination or chimeric antigen receptor-T (CAR-T) cell therapy to treat rGB patients, and successes with antibodies targeting other inhibitory checkpoints or costimulatory molecules have also been reported. These successes inspired us to explore candidate combination treatments based on anti-PD-1/PD-L1 antibodies. However, effective predictive biomarkers for clinical efficacy are urgently needed to avoid economic waste and treatment delay. Attempts to prolong the CAR-T cell lifespan and increase T cell infiltration through engineering techniques are addressing the challenge of strengthening T cell function. In this review, we describe the immunosuppressive molecular characteristics of rGB; clinical trials exploring anti-PD-1/PD-L1 therapy, tumor-specific peptide vaccination, and CAR-T cell therapy; candidate combination strategies; and issues related to strengthening T cell function.

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