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(1) Folate receptor α (also known as FR α, FOLR1) is a 38-40 kDa glycosylphosphatidylinositol (GPI) expressed in a variety of epithelial tissues, including choroid plexus, lung, thyroid, kidney, uterus, breast, fallopian tube, epididymis and salivary gland. There are four subtypes in human body of folate high-affinity receptors: α, β, γ and δ. The folate receptor circulates repeatedly between the extracellular cavity and the endocytic cavity, and can transport folate into the cell.
(2) FR α is overexpressed on the surface of tumor cells of various cancer types, but it is limited in normal tissues. For example, up to 90% of ovarian cancer express FR α. However, there is almost no expression in non-malignant ovarian tissue, making FR α become a potential tumor target.
2. Excellent preclinical results:
(1) The vitro showed that the BsAb can be binding with hFR α and cynoFR α as high affinity, and no cross reaction with rFRα, also do not combine with FRβ、 FRγ、 FRδ.
(2) The Fab and VHH of the BsAbs can recognize different epitopes of human FRα.
(3) The internalization efficiency of the BsAbs is higher than that of the positive control mirvetuximab, with weak CDC effect and no ADCC effect.
(4) Anti-Fab humanized IgG and VHH of the BsAbs showed high target affinity.
(5) In vitro experiments show that BsAbs-ADC can effectively kill the expression of FRα Cell (HEK293T-FR α cells). In vivo experiments show that BsAbs-ADC has excellent tumor inhibition effect.
1. Asset type: FRαBsAb-ADC
2. Indication: Ovarian cancer
4. Cooperation: sequence authorization or project transfer
5. Research progress:
(1) Ongoing Preclinical research:
FRα bispecific antibody can be developed to treat ovarian cancer.
In vitro, BsAbs showed good affinity and stability.
In vivo, BsAbs-ADC showed good tumor inhibition ability.
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