Triad of co-stimulatory molecules (TRICOM) (TRICOM)

The Triad of co-stimulatory molecules (TRICOM) is a synergistic combination of three proteins—B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58)—designed to enhance the activation and expansion of T cells. In the context of cancer immunotherapy, TRICOM is typically delivered via recombinant viral vectors, such as vaccinia or fowlpox, alongside tumor-associated antigens to overcome the immunosuppressive environment of the tumor. Each component of the triad plays a distinct role: B7-1 provides the primary costimulatory signal by binding to CD28 on T cells, ICAM-1 facilitates stable adhesion between T cells and antigen-presenting cells via LFA-1, and LFA-3 interacts with CD2 to further lower the threshold for T-cell activation. Together, these molecules provide a potent Signal 2 that significantly amplifies the immune response compared to the use of any single costimulatory molecule. TRICOM-based vaccines have been extensively evaluated in clinical trials for various malignancies, most notably in the PROSTVAC vaccine for prostate cancer and the PANVAC vaccine for solid tumors expressing CEA and MUC-1. While these therapies aim to generate a durable anti-tumor immune response, they are generally well-tolerated, with common side effects limited to injection site reactions and transient flu-like symptoms. The strategy represents a sophisticated approach to licensing the immune system to recognize and destroy cancer cells that would otherwise evade detection due to a lack of endogenous costimulatory signals.

Other names

B7-1/ICAM-1/LFA-3 triadTRICOM complexT-cell co-stimulatory triadTriad of co-stimulatory molecules

Enhancement of T-cell activation by providing three distinct costimulatory signals (B7-1, ICAM-1, and LFA-3) simultaneously to lower the activation threshold and promote robust anti-tumor immunity.