Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Clinical studies include:
- A phase II trial testing the HSPPC-96 vaccine in patients with recurrent glioma that can be removed with surgery (NCT01814813).
- A phase I trial testing two adenoviral vectors, with one testing HSV1-TK, which is expected to kill brain cells and expose the tumor antigens, and one testing Flt3L, a cytokine known to cause proliferation of dendritic cells, in patients with newly diagnosed high grade glioma (NCT01811992).
- A phase I trial testing a personalized cancer vaccine, NeoVax, in adult patients with MGMT-unmethylated, newly diagnosed glioblastoma (NCT02287428).
- A phase I trial testing ADU-623, a vaccine targeting the EGFRvIII and NY-ESO-1 antigens, in patients with treated and recurrent grade III/IV astrocytomas (NCT01967758).
- A phase I trial testing a dendritic cell vaccine for patients with newly diagnosed or recurrent glioblastoma (NCT02010606).
- A pilot study to test glioma antigen peptides given along with Poly-ICLC (Hiltonol®), a Toll-like receptor 3 agonist, in pediatric patients with glioma (NCT01130077).
- A pilot study testing glioma antigen peptides given along with imiquimod, a Toll-like receptor 7/8 agonist, in children with recurrent ependymomas (NCT01795313).
- A pilot study testing a tumor vaccine that targets the brain tumor initiating cell (BTIC) line given along with imiquimod, a Toll-like receptor 7/8 agonist, in adult patients with grade II gliomas (NCT01678352).
A promising avenue of clinical research in brain cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances on immune responses. By blocking these inhibitory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. The following trials are currently recruiting patients with brain cancer:
- A phase III trial of nivolumab (Opdivo®), versus temozolomide (Temodar®), with radiation therapy for patients with newly-diagnosed glioblastoma (NCT02617589).
- A phase II trial testing durvalumab (MEDI4736), an anti-PD-L1 antibody, in patients with glioblastoma (NCT02336165). This trial is sponsored by Ludwig Cancer Research in partnership with the Cancer Research Institute.
- A phase I trial of nivolumab (Opdivo®) +/- a dendritic cell vaccine in patients with recurrent glioma, astrocytoma, or glioblastoma (NCT02529072).
Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.
- A phase II/III trial testing Toca 511 (vocimagene amiretrorepvec), which is based on the mouse leukemia virus and made to encode the gene cytosine deaminase, and Toca FC, an oral drug, versus the standard-of-care for patients with recurrent glioblastoma multiforme or anaplastic astrocytoma who are undergoing surgery (NCT02414165). There is also a phase I trial testing Toca 511/Toca FC combined with the standard-of-care for patients with newly diagnosed high grade glioma (NCT02598011).
- A phase I trial testing DNX-2401 in patients with recurrent glioblastoma or gliosarcoma (NCT02197169).
- A phase I trial testing a measles virus that produces carcinoembryonic antigen (CEA) in patients with recurrent glioblastoma multiforme (NCT00390299).
- A phase I trial testing the herpes simplex virus HSV-1716 in pediatric patients with refractory or recurrent high grade gliomas that can be removed with surgery (NCT02031965).
- A phase I trial testing a genetically engineered poliovirus for adult patients with recurrent glioblastoma multiforme (NCT01491893).
In this approach, immune cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Clinical trials include:
- A phase I/II trial testing anti-EGFRvIII chimeric antigen receptor (CAR) T cells in patients with malignant glioma (NCT01454596).
Adjuvants are substances that boost the immune response. They can be used alone or combined with other immunotherapies.
- A phase II trial testing Poly-ICLC (Hiltonol®), a Toll-like receptor 3 agonist, in patients with recurrent pediatric grade I or II astrocytoma (NCT01188096).
- A phase I/II trial testing indoximod, an IDO inhibitor, in patients with recurrent glioma (NCT02052648).
- A phase I trial of indoximod and temozolomide (Temodar®) for pediatric patients with brain cancer (NCT02502708).
Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors.
- A phase II trial of ABT-414, an antibody-drug conjugate (ADC) that targets EGFR/EGFRvIII, in patients with newly diagnosed glioblastoma (NCT02573324).