Current Vaccine Trials in Glioblastoma: A Review

Table 1

Vaccine strategies.

Products	Comments
Whole tumor cell	Broad range of antigens, known and unknown
	Autologous	Patient-specific, customized, and of high cost of production
	Allogeneic	Based on one or more tumor cell lines, “off the shelf,” and easier to produce
	Genemodified	Increase antitumor immunity, cytokine expression (IL-2, GM-CSF), and costimulatory molecules (B7-1)
Dendritic cell	Most potent antigen presenting cell, highly specialized culture techniques
	Tumor pulsed	Broad array of antigens
	Peptide/protein pulsed	Single or combination of antigens targeted, highly specific
	Genemodified	Expression of cytokines or costimulatory molecules to enhance immunogenicity
Protein	Single or combination, potential for autoimmunity
Peptide	Minimize autoimmunity associated with whole protein and are easy to produce, cost-effective, and able to enhance immunogenicity and to quantify peptide specific T cell response with tetramer
Heat-shock proteins	Purified from tumor cells, immune response to peptides carried by the HSPs
Other	Viral and bacterial vectors, plasmid DNA
Adjuvants
TLR agonists	IFA (incomplete Freund’s adjuvant), BCG, LPS (lipopolysaccharide), RNA, CpG DNA motifs, and MPL (monophosphoryl lipid A)
Cytokines	IL-2, GM-CSF
Costimulatory molecules	B7-1, B7-2, and CD40
Delivery
Intradermal	Easy to administer and requires migration of DCs to draining lymph node or scavenging of antigens by endogenous DCs
Intranodal	Theoretical advantage of bypassing need for lymph node migration, possible destruction of LN architecture, and questionable benefit
Intratumoral	Enhance immunogenicity of tumor and may not be feasible for brain tumors
Combinatorial strategies
STAT3 inhibition	Reverse tumor induced STAT3 mediated immunosuppression
PD-1 blockade	Enhance CD8 T cell function, effective in non-small-cell lung CA, melanoma, and renal cell CA
Chemotherapy and radiation	Potential for upregulation of tumor antigens and MHC and decreased tumor burden