Table 1.
Platform | Rationale | Immunogenicity | Toxicity | HLA Restriction | Pros | Cons |
---|---|---|---|---|---|---|
Peptide – Based | Elicit immunity to tumor associated self-antigens or tumor specific antigens | Low | Low | Yes | • Easy to produce with high purity in large amounts (e.g., cost effective) | • Only target one or a few epitopes – needs multiple peptides to prevent immune escape |
• High specificity through use of defined epitopes | ||||||
• Immunological compatibility only in patients with a specific HLA subtype. | ||||||
• No additional treatments/procedures for patients | ||||||
• Not pharmacologically active (little toxicity) | • Peptides with low affinity for MHC may be poorly immunogenic | |||||
• Repeated booster vaccines to help with sustained immune response | ||||||
• Immune responses may be transient or of low magnitude | ||||||
• Often requires that it is given with immunoadjuvant to enhance immunogenicity | ||||||
Protein – Based | Elicit immunity to tumor associated self-antigens or tumor specific antigens | Moderate | Low | No | • Multiple epitopes | • Give with immunoadjuvant to enhance immunogenicity |
• More costly than peptide-based vaccines | ||||||
• Higher antigen load | ||||||
Viral – Based | Use natural ability to trigger immune responses and carry genetic material into cells for production of antigens | High | High | No | • Introduce target antigen into immune cells | • Immune response against priming virus requires different virus for a booster |
• Easy to produce on large scale | ||||||
Bacteria – Based | Use natural ability to trigger immune responses and carry genetic material into cells for production of antigens | High | High | No | • Effective antigen delivery – express foreign antigens | • Risk of undesired infections (but may be treated with antibiotics) |
• Stimulate mucosal and systemic responses | ||||||
• Easy to produce on large scale | ||||||
Dendritic Cells/ Antigen Presenting Cells | DC's are the body's most effective APCs Can have protein, peptide or viral infected cells | High | Low | Yes | • More control over APC stimulation and antigen presentation | • Logistically difficult (APC selection, ex vivo maturation) |
• HLA restricted but autologous cells | • Expensive – collection and manipulation | |||||
• Need for a leukapheresis facility | ||||||
• Risk of leukapheresis (central line insertion, hypotension, electrolyte imbalances, vascular injury) | ||||||
• Difficult to ensure consistent vaccine production (varying leukapheresis yields, varying activated APCs, possible bacterial contamination) | ||||||
Whole Tumor Cells | Deliver multiple relevant tumor antigens | Moderate | Low | No | • Broad array of antigens represented (minimizes immune escape) | • Cancer cells themselves are not that immunogenic |
• Autologous cell vaccines are labor-intensive and difficult to standardize | ||||||
• Readily produce allogenic cell lines on larger scale | ||||||
• Not HLA restricted due to whole proteins present |
HLA Restriction – Different HLA subtypes present different antigens. Antigen is only immunological comparable in patients with a specific HLA subtype (i.e., HLA-A2+)