TABLE 1.
Immunotherapeutic strategies tested in patients with GBM.
| Immunotherapy | Strengths | Weaknesses | Applied to GBM patients | References |
| Antibodies | High specificity and affinity Low cost |
Low efficacy Limited ability to cross BBB Off target toxicity |
Bevacizumab (anti-VEGF) Nimotuzumab (anti-EGFR) Cetuximab (anti-EGFR) |
Neyns et al., 2009; Westphal et al., 2015; Lombardi et al., 2017 |
| Adoptive effector cell transfer | Ex vivo stimulation and expansion of tumor cell targeting immune cells Safe (auto) |
Poor survival and proliferation Poor trafficking to tumor sites Risk of GvHD (allo) |
Allogeneic T cells Autologous T cells Autologous lymphokine-activated killer cells Autologous tumor infiltrating lymphocytes |
Quattrocchi et al., 1999; Weenink et al., 2020 |
| CAR T cells | Specificity HLA independent Long term proliferation and survival (‘Living drug’) |
Costly and time-consuming manufacture Potential toxicity Acquired resistance |
EGFRvIII-specific CAR T cells HER2-specific CAR T cells IL13Rα2-specific CAR T cells |
Brown et al., 2015; Ahmed et al., 2017; Goff et al., 2019 |
| Checkpoint Inhibitors | Easily applicable Proven response in certain subsets of patients |
Reliant on cognate T cells Reliant on HLA class I APM function in cancer cells Variable response Lack of markers to identify potentially responding patients |
Pembrolizumab (anti-PD-1) Nivolumab (anti-PD-1) Nivolumab and ipilimumab (anti-CTLA-4) Durvalumab (anti-PD-L1) Avelumab (anti-PD-L1) |
Cloughesy et al., 2019; Schalper et al., 2019; Reardon et al., 2020 |
| Oncolytic Viruses | Specificity Low toxicity | Low anti-tumor efficacy Dependent on enhancement of host immune system response Dependent on cancer cell susceptibility to the induced effector mechanism |
HSV-1 M032 DNX-2401 AdV-tK Reolysin G207 |
Markert et al., 2000; Forsyth et al., 2008; Patel et al., 2016; Kieran et al., 2019; Philbrick and Adamson, 2019 |
| Vaccines | Specificity Safe Patient specific Ability to target multiple TAs |
Variable immune response Reliant on cognate T cell efficacy (HLA restricted) Identification of immunogenic source required Can be costly |
Peptide vaccines: Autologous peptides EGFRvIII protein Multiple tumor antigens Survivin Dendritic cell vaccines: Tumor lysate Glioma stem like cell antigens |
Weller et al., 2017; Liau et al., 2018; Weenink et al., 2020 |