Molecular screening and neoantigen cloning - Fundamental of adoptive T-cell immunotherapy

Authors: ZHANG, WEI - Case Western Reserve University (CWRU); Liu, Ge - George; DEVEMY, EMMANUELLE - Rush University; LI, BIAORU - Augusta University

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 11/3/2020
Publication Date: 11/3/2020
Citation: Zhang, W., Liu, G., Devemy, E., Li, B. 2020. Molecular screening and neoantigen cloning - Fundamental of adoptive T-cell immunotherapy (Chapter 6). In: Li, B., Larson, A., Li, S. editors. Personalized Immunotherapy for Tumor Diseases and Beyond. Singapore, Singapore: Bentham Science Publishers Pte. Ltd. p. 80-96.

Interpretive Summary: Molecular characrterization of tumor antigens will facilitate immunotherapy. We provided an overview of screening tumor antigens using molecular biology techniques. These results fill our knowledge gaps and provide the foundation for incorporating new biological insights into immunotherapy. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enabled animal selection will benefit from these biological knowledges.

Technical Abstract: Specific T-cells, TCR T-cells, and CAR-T-cells require to establish some techniques of molecular biology to support them, including screening tumor-associated antigen (TAA)/tumor specific antigen (TSA) and mutant proteins/peptides; constructing an expression system; packaging an expression vector. The molecular biology technique is a very important in targeting neoantigens for tumor-specific T-cells of adoptive T-cell immunotherapy. Since tumor cells often accumulate hundreds of mutations and harbor several immunogenic neoantigens, the repertoire of mutant protein or neoantigen from patient tumor cells might need to screen and discover the antigens for engineering specific T-cells, TCR T-cells, and CAR T-cells. In order to understand the procedures for T-cell adoptive immunotherapy based on molecular biology techniques for mutant proteins and neoantigens from an individual patient, in this chapter, we focus on streamlining of screening tumor antigens (TAA or TSA) and mutant proteins (proteins or peptides), constructing an expression and packaging system with the expression. Moreover, because the three T-cells are distinct from their development and clinical application, we first introduce their research and development (R&D). These methodologies are increasingly supporting clinical oncologists to apply to T-cell immunotherapy. The chapter aims to present fundamental of molecular biology for adoptive T-cell immunotherapy of clinical patients.