Teritusumab combination regimen: Can PD-1 reverse T cell exhaustion?

Teritusumab (Teclistamab-cqyv), as a bispecific T cell engaging antibody targetingB cell maturation antigen (BCMA) and CD3, has attracted widespread attention in the treatment of multiple myeloma (MM). Its mechanism of action is to guide the patient's own T cells to combine with tumor cells, thereby achieving T cell activation and inducing tumor cell lysis. However, under long-term treatment or under high tumor burden, T cells often experience a state of "T-cell exhaustion", which is manifested by loss of function, reduced cytokine release, and reduced cytotoxic activity, which directly limits the long-term efficacy of teritusumab.

PD-1 (programmed death receptor 1), as a core marker of T cell exhaustion, plays an important role in chronic viral infection and tumor immune evasion mechanisms. Therefore, combining teritusumab with PD-1 inhibitors has become a promising combination immunotherapy strategy. By blocking the PD-1/PD-L1 pathway, the "brake" of T cells can be effectively released and their killing activity restored, which can theoretically enhance the anti-tumor effect mediated by teritusumab.

In multiple overseas early exploratory studies and immune mechanism experiments, it was found that PD-1 inhibitors such as Pembrolizumab or Nivolumab combined with teritutumab can promote the functional recovery of CD8+ T cells and enhance their response strength in the myeloma microenvironment. In addition, after long-term use of teritusumab, some patients' T cells can upregulate PD-1 expression due to continued antigen stimulation. Adding a PD-1 inhibitor at this time can not only delay depletion, but also reverse certain drug-resistant phenotypes, especially for patients with poor response or relapse.

However, there are challenges to joint use, particularly in terms of security. Teritusumab is known to induce cytokine release syndrome (CRS) and immune-related neurotoxicity (ICANS), while PD-1 inhibitors can also induce autoimmune inflammatory reactions. The combined use of the two may increase the risk of immune system hyperactivity and needs to be implemented with caution and under high monitoring.

Reference materials:https://www.tecvayli.com/