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The potential applications of T cell receptor (TCR)-like antibody in cervical cancer immunotherapy.

ABSTRACT: Cervical cancer is ranked as the fourth most common cancer in women worldwide. Monoclonal antibody has created a new dimension in the immunotherapy of many diseases, including cervical cancer. The antibody's ability to target various aspects of cervical cancer (oncoviruses, oncoproteins, and signaling pathways) delivers a promising future for efficient immunotherapy. Besides, technologies such as hybridoma and phage display provide a fundamental platform for monoclonal antibody generation and create the opportunity to generate novel antibody classes including, T cell receptor (TCR)-like antibody. In this review, the current immunotherapy strategies for cervical cancer are presented. We have also proposed a novel concept of T cell receptor (TCR)-like antibody and its potential applications for enhancing cervical cancer therapeutics. Finally, the possible challenges in TCR-like antibody application for cervical cancer therapeutics have been addressed, and strategies to overcome the challenges have been highlighted to maximize the therapeutic benefits.

SUBMITTER: Dass SA

PROVIDER: S-EPMC8381793 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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The potential applications of T cell receptor (TCR)-like antibody in cervical cancer immunotherapy.

Dass Sylvia Annabel SA Selva Rajan Rehasri R Tye Gee Jun GJ Balakrishnan Venugopal V

Human vaccines & immunotherapeutics 20210514 9

Cervical cancer is ranked as the fourth most common cancer in women worldwide. Monoclonal antibody has created a new dimension in the immunotherapy of many diseases, including cervical cancer. The antibody's ability to target various aspects of cervical cancer (oncoviruses, oncoproteins, and signaling pathways) delivers a promising future for efficient immunotherapy. Besides, technologies such as hybridoma and phage display provide a fundamental platform for monoclonal antibody generation and cr ...[more]

PMID: 33989511

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Project description:Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system. Cytotoxic T-cells are regularly involved in surveillance and are capable of both eliminating diseased cells and generating protective immunological memory. The specificity of a given T-cell is determined through the structural interaction between the T-cell receptor (TCR) and a peptide-loaded major histocompatibility complex (MHC); i.e., an intracellular peptide-ligand displayed at the cell surface by an MHC molecule. However, a given TCR can recognize different peptide-MHC (pMHC) complexes, which can sometimes trigger an unwanted response that is referred to as T-cell cross-reactivity. This has become a major safety issue in TCR-based immunotherapies, following reports of melanoma-specific T-cells causing cytotoxic damage to healthy tissues (e.g., heart and nervous system). T-cell cross-reactivity has been extensively studied in the context of viral immunology and tissue transplantation. Growing evidence suggests that it is largely driven by structural similarities of seemingly unrelated pMHC complexes. Here, we review recent reports about the existence of pMHC "hot-spots" for cross-reactivity and propose the existence of a TCR interaction profile (i.e., a refinement of a more general TCR footprint in which some amino acid residues are more important than others in triggering T-cell cross-reactivity). We also make use of available structural data and pMHC models to interpret previously reported cross-reactivity patterns among virus-derived peptides. Our study provides further evidence that structural analyses of pMHC complexes can be used to assess the intrinsic likelihood of cross-reactivity among peptide-targets. Furthermore, we hypothesize that some apparent inconsistencies in reported cross-reactivities, such as a preferential directionality, might also be driven by particular structural features of the targeted pMHC complex. Finally, we explain why TCR-based immunotherapy provides a special context in which meaningful T-cell cross-reactivity predictions can be made.

Dataset Information

The potential applications of T cell receptor (TCR)-like antibody in cervical cancer immunotherapy.

Publications

The potential applications of T cell receptor (TCR)-like antibody in cervical cancer immunotherapy.

Similar Datasets

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