pMHC-targeted TCRm Antibody Assessment and Validation

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TCRm antibodies have been developed as a new class of antibodies that can target intracellular antigens and recognize peptides loaded on MHC molecules with higher specificity and affinity than TCR. In order to advance the development and application of TCRm antibodies targeting novel MHC-restricted peptides, their specificity and biological activity should be validated. Creative BioMart provides multiple techniques to validate the cross-reactivity and specificity of TCRm antibodies targeting pMHC to achieve superior anti-tumor efficacy and safety so that TCRm antibodies can be used in future clinics as soon as possible.

Characterization of pMHC-targeted TCRm Antibodies

Fig.1 Schematics of TCR and TCRm antibodies (He Q, et al., 2019)

TCRm antibodies are a new family of antibodies that, like TCRs, recognize pMHC complexes on the surface of tumor cells. The effective use of TCRm antibodies for cancer treatment must overcome many obstacles, including low pMHC epitope density, identification of suitable antigenic targets, cross-reactivity of MHC molecules, high specificity, and high affinity characteristics are all potential issues that need to be addressed.

The main concerns for TCRm-based antibody therapies include their specificity for peptides presented by MHC molecules and their cross-reactivity with other structurally related or unrelated peptides, and also their specific anti-tumor activity. These are important features that need to be clearly understood and validated before we can put them into clinical use.

Our Solutions

TCRm antibodies require systematic validation to characterize their cross-reactivity, specificity and anti-tumor activity. We offer a range of technical services for the evaluation and validation of TCRm antibodies.

Detection of the ability of TCRm antibody to bind pMHC on cells
The ability of the TCRm antibody to bind pMHC complexes can be assessed by fluorescence-activated cell sorting (FACS) using flow cytometry, and the data obtained from the fluorescence analysis are analyzed using software.
Cytotoxicity assay of TCRm antibody
Tumor cells will be incubated with the antibody in medium, and specific tumor cell killing will be determined by absorbance assessment of the supernatant, and specific cytotoxicity of the antibody will be calculated.
Cross-reactivity study
The cross-reactivity and specificity of TCRm antibodies can be determined using a set of cell lines and binding of peptide pulsed T2 cells, or directly by crystallographic studies to fully characterize TCRm antibodies and detailed biochemical assessment to explain the mechanism of their recognition of other peptides with sequence similarity to the target peptide.
In vitro and in vivo evaluation of antitumor activity
Exposure of pMHC complex-positive and negative cell lines to TCRm antibodies is used to assess their in vitro antitumor activity, as well as to monitor the antitumor activity and toxicity of antibody drugs using xenograft models.

What We Achieve for Our Customers

We evaluate and validate our clients' carefully designed antibodies through a variety of research techniques, studying their safety and biological activity through multiple in vitro and in vivo pathways, paving the way for successful clinical treatment of a wide range of cancers.

Assessment of cross-reactivity and specificity of specific TCRm antibodies targeting pMHC.
Validation of the antitumor efficacy and safety of specific TCRm antibodies targeting pMHC.

Creative BioMart provides specific evaluation and validation solutions for each client to develop TCRm antibodies against different antigenic targets presented by MHC. The specific assay or service you need is not available above, please feel free to contact us to provide you with additional service offerings.

References

He Q, et al. "TCR-like antibodies in cancer immunotherapy." J Hematol Oncol (2019),12(99).
Kurosawa N, et al. "Development of a T-cell receptor mimic antibody targeting a novel Wilms tumor 1-derived peptide and analysis of its specificity." Cancer science (2020), 111(10): 3516-3526.

For research use only. Not for clinical use.