4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer

Abstract

The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

“…A previous study using vaccina virus characterized virus-specific precursors and determined their necessity to confer protective T cell immunity [ 36 ]. Thus, the important finding of fewer epitope-specific precursor CD8 + T cells in our model in uninfected aged mice further supports and underscores an age-dependent diminished virus-specific CD8 + T cell response to HMPV infection [ 30 , 37 ].…”

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

“…An alternative platform for testing CD40 agonism is LOAd703, an oncovirus expressing trimerized CD40L and 4-1BB, another member of the TNF family [ 155 ]. LOAd703 is currently being evaluated in combination with standard chemotherapy in patients with advanced solid tumors including pancreatic cancer (NCT03225989).…”

Engineering an active immunotherapy for personalized cancer treatment and prevention of recurrence

“…S3, D and E). 4-1BBL has been reported to be the most effective signaling molecule for activating lymphocytes ( 34 ), and CD40L is known to maintain full activation of T cells ( 35 ). Accordingly, we hypothesized that this p13nsEV which expresses costimulatory factors induced by LPS/STING agonist combination treatment will have an enhanced ability to activate T cells.…”