| Anti-tumor mAb |
Unmodified IgG or IgG modified to mediate enhanced ADCC |
Tumor-associated surface antigen |
Are IgGs with enhanced affinity for Fc receptors more effective clinically than unaltered IgG? |
| Angiogenesis inhibition |
Unmodified IgG |
Host molecules that control angiogenesis |
What is the best way to evaluate clinical response in patients treated with angiogenesis inhibitors? |
| T cell checkpoint blockade |
IgG1 (blocks checkpoint and mediates ADCC) or IgG4 (blocks checkpoint without mediating extensive ADCC) |
Molecules that limit the anti-cancer T cell response |
How should we combine checkpoint blockade mAbs with each other, other immunotherapeutics, and other anti-cancer agents? |
| Radioimmuno-therapy |
Unmodified IgG or mAb fragment |
Tumor-associated antigen that is not shed or present in circulation |
How can the logistics of administering successful radioimmunotherapeutic agents be simplified to enhance their clinical utility? |
| Antibody-drug conjugate |
IgG modified with cleavable linker and drug |
Highly specific tumor-associated antigen that can internalize when bound by mAb |
What is the best combination of linkers and drugs with each mAb and target antigen? |
| Bifunctional antibody |
Variable regions from cancer-specific mAb linked to variable region specific for activating receptor on T cell |
Tumor-associated antigen that is not commonly absent in antigen-loss resistant variants |
Can bispecific constructs be developed that are effective and have modified kinetics thereby avoiding the logistic complexities of continuous infusion? |
| Chimeric antigen receptor T cell |
Gene therapy approach to modifying T cells by inserting DNA coding for the mAb variable region fused to signaling peptides |
Highly tumor-specific antigen that is not commonly absent in antigen-loss resistant variants |
Can very promising preliminary results be extended to solid tumors or will toxicity be associated with expression of low levels of target antigen by benign cells? |
