Tissue Cross-Reactivity Studies

Antibody drugs are a hot spot in the field of biopharmaceutical research and development today. For such candidate drugs, Creative Biolabs provides tissue cross-reaction research services to assist clients in drug development.

Definition and Research Significance of Tissue Cross-Reactivity

Tissue cross-reactivity refers to the phenomenon in which antibodies bind to multiple similar or related antigens in vitro. This cross-reactivity may trigger non-specific immune responses or produce unwanted side effects. Therefore, in biomedical research and drug development, tissue cross-reactivity analysis for candidate antibody drugs is very important. This analysis can assess the cross-reactivity of candidate antibody drugs with other antigens, providing important references for multiple aspects of drug development.

Specificity optimization	Safety assessment	Individual difference assessment
The specificity of candidate antibody drugs is one of the important indicators for drug development. Tissue cross-reaction research can help determine the selectivity of antibody drugs and target antigens, and help the further screening of specific antibodies or optimize the design and structure of antibodies to improve the specificity and therapeutic effect of candidate antibody drugs.	Tissue cross-reactivity studies can evaluate the interaction of candidate antibody drugs with molecules in different tissues, help predict potential adverse reactions and safety risks, and ensure drug safety.	Different individuals may have different responses to antibody drugs. Through tissue cross-reaction studies, the effects of drugs in different individuals are understood, providing an optimization basis for improving the therapeutic effect of candidate drugs.

Core Technology Applied to Tissue Cross-Reaction

Immunohistochemical (IHC)

Fig.1 Multiplex IHC staining to evaluate the level of α-SMA in 4T1-hPD-L1 tumors.¹

In the tissue cross-reactivity test of candidate antibody drugs, Creative Biolabs can provide different physiological or disease models, including 3D spheroid model, organ-on-a-chip model, 3D ex vivo human tissue model, precision-cut tissue slice model, to test the tissue cross-reactivity of candidate antibody drugs in a microenvironment closer to the real human body. Tissue or cell processing methods are divided into chemical fixation and freezing. We recommend that you choose the freezing first.

Method	Chemical Fixation	Freezing method
Introduction	The chemical fixation method is to fix the tissue sample in a certain state by using chemical reagents to maintain the tissue structure and the immunological activity of the antigen. Commonly used chemical reagents include formalin and glutaraldehyde.	The freezing method is to quickly freeze tissue samples at extremely low temperatures to maintain the morphology and structure of the tissue and the immunological activity of the antigen. Freezing usually uses extremely low-temperature freezing media such as liquid nitrogen or dry ice.
Advantage	Excellent tissue retention Antigen retention	Quick fix Suitable for active antigens
Shortcoming	Longer fixed time Affected solubility of antigen	Limited tissue retention Freezing damage

Comprehensive Tissue Cross-Reactivity Assay at Creative Biolabs

Creative Biolabs provides one-step and two-step tissue cross-reactivity research services. The two methods differ in the steps of antigen-antibody reaction and signal amplification.

Method	One-step IHC	Two-step IHC
Feature	Antigens are detected directly	Indirect detection of antigens.
Introduction	The primary antibody directly binds to the target antigen and is present in the staining reaction together with a label such as an enzyme label or a fluorescent label.	After the primary antibody binds to the target antigen, the secondary antibody is added, which binds to the primary antibody and carries a label (such as an enzyme label or a fluorescent label) for signal amplification.
Advantage	Simple and fast Wide application range Direct visualization	Signal amplification Low background signal
Shortcoming	Limited signal amplification High background signal	Complicated operation Potential cross-reactivity

If you need to test the safety and specificity of candidate antibody drugs in the preclinical research stage, please feel free to contact us. We are already here to provide reliable assistance.

Reference

Yi, M.; et al. Anti-TGF-β/PD-L1 bispecific antibody promotes T cell infiltration and exhibits enhanced antitumor activity in triple-negative breast cancer. Journal for Immunotherapy of Cancer. 2022, 10(12).

Research Model

3D Biology Based Biomarker Discovery

3D Biology Based Drug Discovery and Development

3D Biology Based Toxicity Evaluation

Supporting Assays

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