This article discusses the potential of immune co-stimulation in enhancing immune activation and destabilizing the immunosuppressive tumor microenvironment. It focuses on CD137, a potent immune costimulatory receptor, and the development of a recombinant 4-1BBL protein for soluble co-stimulatory activity. The treatment with SA-4-1BBL shows promising results in inhibiting lung tumor development in mice.
Immunotherapy utilizing checkpoint inhibitors has shown remarkable success in the treatment of cancers. In addition to immune checkpoint inhibitors, immune co-stimulation has the potential to enhance immune activation and destabilize the immunosuppressive tumor microenvironment. CD137 , also known as 4-1BB , is one of the potent immune costimulatory receptors that could be targeted for effective immune co-stimulation.
The interaction of the 4-1BB receptor with its natural ligand (4-1BBL) generates a strong costimulatory signal for T cell proliferation and survival. 4-1BBL lacks costimulatory activity in soluble form. To obtain co-stimulatory activity in soluble form, a recombinant 4-1BBL protein was generated by fusing the extracellular domains of murine 4-1BBL to a modified version of streptavidin (SA-4-1BBL). Treatment with SA-4-1BBL inhibited the development of lung tumors in A/J mice induced by weekly injections of the tobacco carcinogen NNK for eight week
Immunotherapy Checkpoint Inhibitors Immune Co-Stimulation CD137 4-1BB 4-1BBL Lung Tumors Cancer Treatment
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