|
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 |
|