Selective expression of the target antigen on tumors relative to normal tissues provides the basis for ADC targeting to tumors and minimizes the potential for targeted toxicity in normal tissues. The abundance of the target antigen on the cell surface and its distribution in the tumor (homogeneous vs heterogeneous expression) can be important determinants of ADC efficacy.
BOC Sciences provides a comprehensive set of ADC development services for targeted drug discovery, our professional scientists have extensive experience in antibody modification, small molecule synthetic chemistry, and bio-conjugation and are committed to providing high-quality services to promote the development of innovative cancer treatments. We have a dedicated custom development platform that is very convenient for our customers to customize different ADC products and services.
Improvement of ADC safety and efficacy profiles relies significantly on selection of the target antigen and its interaction with the mAb of the ADC. Two critical parameters involved in the selection of the target antigen are tumor specificity and expression level. Ideally, the chosen target will exhibit a high level of tumor-specific or disease-specific expression and be minimal to absent in normal tissues. Specificity of the target is critical to reducing toxicity of ADCs, and thus plays a substantial role in their overall success. For oncological indications, the antigen can be expressed as a surface receptor on tumor cells, tumor stem cells, or within the tumor vasculature and microenvironment. In best cases, the antigen will also be expressed homogenously across tumor cells at similar levels. ADCs with sufficient control of bystander effect may overcome the challenge of heterogenous cell populations within a tumor.
A subset of candidate ADC targets not only show differential expression in tumors compared to normal tissues but also play a biological role in the growth or survival of tumor cells. Attachment to secreted or shed antigen can alter the pharmacokinetics of an ADC and potentially limit effective targeting of tumors. ADC effectiveness ultimately reflects a combination of target antigen properties including antigen density, internalization and intracellular processing, and sensitivity of the target cell to the cytotoxic payload. Most tumor-associated antigens are also expressed to some extent on normal tissues. Such antigens can be considered if expression is restricted to tissues that do not present a toxicity concern. For example, ADCs for prostate cancer have targeted PSMA or Prostate Stem Cell antigen (PSMA), which are expressed on normal prostate tissue; gemtuzumab ozogamicin, targets CD33, which is expressed on both malignant and normal cells of myeloid lineage. Certain markers specific for B-cell malignancies targeted by ADCs, CD22, CD19, CD20, CD79b, and CD37, are also expressed on normal B-cells, but their temporary depletion can be tolerated.
A key problem in using small-molecule therapeutics as anticancer chemotherapeuticsis off-target toxicity, since these agents are unable to effectively discern tumour cells from normal, healthy human cells. ADCs are advantageous in this respect because the attachment of the cytotoxic agent to a tumour-targeting antibody allows more targeted treatment. To deliver the cytotoxic drug to the correct cells, scientists from BOC Sciences can utilize advanced antigen screening techniques and related antibody modification processes to increase the binding affinity and specificity of antigens and antibodies. These high-quality custom ADCs are suitable for tasks such as proof-of-concept, target validation, as well as control to provide comparison in efficacy for new ADC development projects. Our full list of ADC-targeting cancer surface antigens include: