The abstract discusses the importance of T cell activation and effector functions in the immune response against
cancer. It highlights that
T cell receptor signaling, or "signal I," is essential but not sufficient; a second signal, "signal II," is also necessary, typically provided by costimulatory receptors like
CD28.
Glofitamab, a
CD20-targeted bispecific antibody, is effective in treating
relapsed/refractory non-Hodgkin Lymphoma (r/r NHL), but some patients do not respond to it alone. To enhance the response,
RG6333, a
CD19-targeted bispecific antibody with a unique CD28 binding moiety, is being studied. It provides a strong but safe "signal II" only in the presence of "signal I," avoiding single-agent activity and
cytokine-release syndrome (CRS).
Preclinical experiments have shown that RG6333, even with reduced CD28 affinity, maintains its potency when combined with glofitamab in vitro and in humanized NSG mice. It does not induce T cell activation or cytokine secretion on its own, unlike
TGN1412, a CD28 superagonist. A treatment regimen involving staggered infusions of glofitamab and RG6333 has been proposed for safety and potency. This combination has led to tumor-free outcomes in a difficult-to-treat tumor model and has been shown to boost T cell infiltration and prolong the response to glofitamab. Alternating RG6333 with another costimulatory agent,
RG6076, has completely prevented tumor relapse during treatment. RG6333 also enhances cytokine secretion and T cell activation in patient samples.
The data support the combination of RG6333 with glofitamab for r/r NHL patients, offering a promising alternative to CAR-T cell therapies. RG6333 is currently being studied in a phase I clinical trial in combination with glofitamab.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
