Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy

Figure 8

4-1BBL/4-1BB. Soluble 4-1BBL or hexameric 4-1BBL is essentially inactive. However, enforced oligomerization using SA-4-1BBL enables 4-1BB activation with a favorable toxicity profile. In contrast, agonistic 4-1BB antibodies potently activate 4-1BB signaling but with dose-limiting toxicity. The selective use of 4-1BB co-stimulatory signaling can potentiate CAR T-cell activity and trigger effective lysis. Further, selective delivery of 4-1BBL using scFv:4-1BBL ensures target antigen-restricted conversion of inactive s4-1BBL into membrane-like and signaling competent 4-1BBL.