Emerging Biomarkers During Clinical Development of Anti-CTLA4 Antibody Therapy

Fig. 24.1

This is a proposed schema for intensive immune monitoring. Flow cytometry can be performed on peripheral blood to analyze multiple parameters for T cell activation/exhaustion markers, regulatory T cells, and MDSCs. If tumor tissue is available, immunohistochemical characterization of the cellular populations present as well as gene expression array or RT-PCR can be performed. For tumor types such as melanoma where the expression of differentiation antigens or cancer-testis antigens occurs at a high frequency, tumor antigen (TA)-specific antibody responses in peripheral blood could be analyzed by ELISA and protein array. TA-specific T cell immune responses can also be characterized in both peripheral blood and the tumor. Immunohistochemistry and/or RT-PCR can also confirm protein or RNA expression of the TA

Current immunological assays vary largely in their ability to consistently correlate immune response to clinical outcome. However, three concurrent phenomena will hopefully move immune monitoring forward: the advent of new immune monitoring techniques, an exponential rise in the number of patients treated with anti-CTLA4 therapies on clinical trials and in standard clinical practice, and an increasing awareness of the imperative to conscientiously and consistently bank patient tumor and blood specimens for these assays. Ultimately, it is hoped that the convergence of all these factors will enable immune monitoring strategies to identify robust and validated biomarkers that are prognostic and/or predictive and which can guide further clinical trial development.

Acknowledgements

This chapter is dedicated to the memory of Dr. Lloyd Old, our mentor and friend and one of the true leaders in investigational cancer immunotherapy. His many profound insights inspired much of our group’s immune biomarker studies.

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