-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Text | pick up shells
Recently, Roche’s semi-annual report disclosed the latest pipeline.
A bispecific antibody RG6189 (RO7300490) that targets FAP-CD40 has entered phase I clinical trials, and Roche has eliminated non-selective CD40 agonists from the pipeline.
selicrelumab
.
The CD40 receptor on antigen-presenting cells (APC) plays a key role in regulating the immune response and triggering the adaptive immune response
.
CD40 agonists can enhance the activation of dendritic cells (DC) and the accompanying tumor-specific T cell activation, making this target a promising target in cancer immunotherapy (CIT)
However, the extensive expression of CD40 caused dose-limiting side effects, such as cytokine release syndrome (CRS) and hepatotoxicity, as well as the extensive expression of CD40 receptors on hematopoietic and non-hematopoietic cells, resulting in sink effects.
Agonistic anti-CD40 molecules exhibit a very short serum half-life, which limits the efficacy of CD40 antibodies
.
If CD40 agonism can be selectively targeted to tumor cells, these limitations can be overcome
Therefore, Roche researchers developed a bispecific FAP-CD40 antibody RO7300490, which induces CD40 agonism only in the presence of fibroblast activation protein alpha (FAP), which is a specific expression in tumor stroma.
Protease
.
The preclinical research data on this product has been published in the journal CLINICAL CANCER RESEARCH
This bispecific antibody is a fully human Ig1 double antibody that contains two CD40 Fv regions
In vitro experiments have shown that RO7300490 triggers effective FAP-dependent APC activation and DC activation leads to enhanced T cell activation
Among 10 hud40tg mice carrying MC38-FAP, 8 induced rapid tumor elimination in the FAP-huCD40 double antibody high-dose group (13.
In addition, studies have shown that the FAP-CD40 double antibody induces tumor growth inhibition in a pancreatic tumor model with low invasion and rich interstitial FAP expression
In terms of safety, the FAP-CD40 double antibody high-dose group is well tolerated in insectivorous monkeys and will not cause CD40-related toxicity
