Application of phage display for T-cell receptor discovery

Ch’ng, Angela Chiew Wen; Lam, Paula Yeng Po; Alassiri, Mohammed; Lim, Theam Soon

doi:10.1016/j.biotechadv.2021.107870

Cited by 13 publications

(7 citation statements)

References 184 publications

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“…For pMHC, which has a low density on the cell surface (e.g., for NY-ESO-1 157-165 /HLA-A*02:01, 10-50 copies per cell [19]), a monovalent molecule with a high affinity is more effective in enriching molecules on the tumor cell side than a bivalent molecule with a low affinity, which requires a mature screening platform to obtain a specific clone with a high affinity. Compared with the TCR platform [20][21][22], the antibody platform is relatively easy to establish. Some researchers have attempted to develop TCR mimic antibodies to target pMHC [23], but most TCR mimic antibodies exhibited a greater degree of cross-reactivity due to the different recognition modes of TCRs and antibodies towards pMHC [24], which was not conducive to overall specificity.…”

Section: Discussionmentioning

confidence: 99%

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy

Li,

Zhao,

Shen

et al. 2024

Biomedicines

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Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells. With the premise of choosing optimal peptides, the final complex peptide–MHC could be the tumor-specific target for TCEs. Here, a novel TCR-directed format of a TCE targeting peptide–MHC was designed named IgG-T-TCE, which was modified from the IgG backbone and prepared in a mammalian cell expression system. The recombinant IgG-T-TCE-NY targeting NY-ESO-1157–165/HLA-A*02:01 could be generated in HEK293 cells with a glycosylated TCR and showed potency in T cell activation and redirecting T cells to specifically kill target tumor cells. We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor–PBMC co-engrafted mouse model without any obvious toxicities.

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Section: Discussionmentioning

confidence: 99%

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy

Li,

Zhao,

Shen

et al. 2024

Biomedicines

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“…Targeted TCR affinity sorting and affinity maturation based on the binding of a given antigen are usually performed using yeast display and phage display technologies; these, combined with the soluble tetrameric, dimeric, and monomeric p-MHC ligands, can be used in high throughput to screen natural high-affinity TCRs, identify libraries of TCR mutants with modified affinity, or validate the affinity of TCRs for specific antigens [ 167 , 258 – 261 ]. A library of stably expressed TCR sentinel mutations can be obtained, and soluble p-MHC ligands can be prepared using high-throughput sorting techniques.…”

Section: Applications and Constraints Of Tcr-t Cellsmentioning

confidence: 99%

“…However, these methods are unable to regulate and predict the complex specific binding or cross-reactivity of antigenic peptides [ 262 ]. In addition, the protein expression and modification capabilities of the cells used to display the libraries remain limited [ 258 ], potentially causing distortion of antigenic peptides.…”

Section: Applications and Constraints Of Tcr-t Cellsmentioning

confidence: 99%

Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy

Shao,

Yao,

Yang

et al. 2024

Exp Hematol Oncol

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Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

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“…The phage has a rod-shaped structure with a length of 1,000 nm and a width of 5 nm ( Zhang X. et al, 2022 ; Figure 2A ). It consists of a single-stranded circular DNA genome of approximately 6.4 kb surrounded by five capsid proteins encoded by nine genes ( Ch'ng et al, 2022 ). Among the capsid proteins, pVIII is suitable for peptide and small protein display, while pIII can be used effectively to display large peptides or proteins despite its low protein copy number ( Alfaleh et al, 2020 ; Jaroszewicz et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Phage-based peptides for pancreatic cancer diagnosis and treatment: alternative approach

Yang

Duan

et al. 2023

Front. Microbiol.

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Pancreatic cancer is a devastating disease with a high mortality rate and a lack of effective therapies. The challenges associated with early detection and the highly aggressive nature of pancreatic cancer have limited treatment options, underscoring the urgent need for better disease-modifying therapies. Peptide-based biotherapeutics have become an attractive area of research due to their favorable properties such as high selectivity and affinity, chemical modifiability, good tissue permeability, and easy metabolism and excretion. Phage display, a powerful technique for identifying peptides with high affinity and specificity for their target molecules, has emerged as a key tool in the discovery of peptide-based drugs. Phage display technology involves the use of bacteriophages to express peptide libraries, which are then screened against a target of interest to identify peptides with desired properties. This approach has shown great promise in cancer diagnosis and treatment, with potential applications in targeting cancer cells and developing new therapies. In this comprehensive review, we provide an overview of the basic biology of phage vectors, the principles of phage library construction, and various methods for binding affinity assessment. We then describe the applications of phage display in pancreatic cancer therapy, targeted drug delivery, and early detection. Despite its promising potential, there are still challenges to be addressed, such as optimizing the selection process and improving the pharmacokinetic properties of phage-based drugs. Nevertheless, phage display represents a promising approach for the development of novel targeted therapies in pancreatic cancer and other tumors.

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Application of phage display for T-cell receptor discovery

Cited by 13 publications

References 184 publications

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy

Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy

Phage-based peptides for pancreatic cancer diagnosis and treatment: alternative approach

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