Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application

Xu, Ruijuan; Du, Shiyao; Zhu, Jianguo; Meng, Fanyan; Liu, Baorui

doi:10.1016/j.canlet.2022.215840

Cited by 20 publications

(19 citation statements)

References 105 publications

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“…In the treatment of solid tumors, although TCR‐T cell therapy has shown specific anti‐tumor effects in basic research and clinical trials, it still faces some problems before the clinical application of TCR‐T, especially the lack of tumor‐specific targets 21 . Target problems manifested explicitly in three aspects: (1) HLA‐I down‐regulation results in the lack of T cell recognition targets on the surface of tumor cells 11,12 ; (2) Antigen peptide mismatch limits the activation of TCR‐T cells; (3) TCR‐T cell reactivity is restricted to tumor antigen presented by HLA molecules, limiting the type of patient.…”

Section: Discussionmentioning

confidence: 99%

Membrane fusogenic nanoparticle‐based HLA‐peptide‐addressing universal T cell receptor‐engineered T (HAUL TCR‐T) cell therapy in solid tumor

Wang

Zhu

et al. 2023

Bioengineering & Transla Med

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T cell receptor‐engineered T (TCR‐T) cell therapy has demonstrated therapeutic effects in basic research and clinical trials for treating solid tumors. Due to the peptide‐dependent recognition and the human leukocyte antigen (HLA)‐restriction, TCR‐T cell therapy is generally custom designed to target individual antigens. The lack of suitable universal targets for tumor cells significantly limits its clinical applications. Establishing a universal TCR‐T treatment strategy is of great significance. This study designed and evaluated the HLA‐peptide‐addressing universal (HAUL) TCR‐T cell therapy based on HLA‐peptide (pHLA) loaded membrance fusogenic deliver system. The pHLA‐NP‐based tumor cell membrane modification technology can transfer the pHLA onto the surface of tumor cells through membrane fusogenic nanoparticles. Then tumor cells are recognized and killed by TCR‐T cells specifically. The HAUL TCR‐T cell therapy technology is a universal technology that enables tumor cells to be identified and killed by specific TCR‐T cells, regardless of the HLA typing of tumor cells.

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Section: Discussionmentioning

confidence: 99%

Membrane fusogenic nanoparticle‐based HLA‐peptide‐addressing universal T cell receptor‐engineered T (HAUL TCR‐T) cell therapy in solid tumor

Wang

Zhu

et al. 2023

Bioengineering & Transla Med

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“…Second, since TCRs have evolved to efficiently detect and amplify antigenic signals, these receptors respond to epitope densities much smaller than required for CAR signaling ( 150 ). In addition, TCR-T cell therapy may result in decreased release of cytokines, which can lead to a low risk of CRS ( 115 ). Compared with CAR-T cells, TCR-T penetrates more easily into solid tumors, while CAR-T usually adheres to the outside of the tumor and does not penetrate easily to the inside ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…In summary, TCR-T cell therapy has shown good potential in both preclinical and clinical studies (8,35,102,107,(114)(115)(116). However, clinical trials evaluating TCR-T for CRC are still in their early phases, and the safety and efficacy of these therapies still face many challenges (43).…”

Section: Tcr-t Therapymentioning

confidence: 99%

Advances in adoptive cellular therapy for colorectal cancer: a narrative review

Yi¹,

Hu²

2022

Ann Transl Med

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Background and Objective: In recent years, adoptive cell therapy (ACT) has shown great potential in antitumor treatment. To significantly improve the clinical efficacy of ACT against solid tumors, we may need to carefully study the latest developments in ACT. As one of the most common malignancies, colorectal cancer (CRC) is a major risk to human health and has become a significant burden on global healthcare systems. This article reviews the recent advances in the treatment of CRC with ACT.Methods: We searched PubMed for articles related to ACT for CRC published as of August 31, 2022, and retrieved relevant clinical trial information on the National Institutes of Health ClinicalTrials.gov website.Based on search results, comprehensive and systematic review is made.

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“…), tumour neoplastic antigens, and cancer testicular antigens (CTAs). The tumour neoplastic antigen TCR-T has achieved promising results in the treatment of a variety of solid tumours [85][86][87]. Those targeting viral proteins mainly include HBV.…”

Section: T Cell Receptor Engineered T Cellmentioning

confidence: 99%

Application of adoptive cell therapy in hepatocellular carcinoma

2023

Immunology

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Hepatocellular carcinoma (HCC) remains a global health challenge. Novel treatment modalities are urgently needed to extend the overall survival of patients. The liver plays an immunomodulatory function due to its unique physiological structural characteristics. Therefore, following surgical resection and radiotherapy, immunotherapy regimens have shown great potential in the treatment of hepatocellular carcinoma. Adoptive cell immunotherapy is rapidly developing in the treatment of hepatocellular carcinoma. In this review, we summarize the latest research on adoptive immunotherapy for hepatocellular carcinoma. The focus is on chimeric antigen receptor (CAR)‐T cells and T cell receptor (TCR) engineered T cells. Then tumour‐infiltrating lymphocytes (TILs), natural killer (NK) cells, cytokine‐induced killer (CIK) cells, and macrophages are briefly discussed. The main overview of the application and challenges of adoptive immunotherapy in hepatocellular carcinoma. It aims to provide the reader with a comprehensive understanding of the current status of HCC adoptive immunotherapy and offers some strategies. We hope to provide new ideas for the clinical treatment of hepatocellular carcinoma.

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Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application

Cited by 20 publications

References 105 publications

Membrane fusogenic nanoparticle‐based HLA‐peptide‐addressing universal T cell receptor‐engineered T (HAUL TCR‐T) cell therapy in solid tumor

Membrane fusogenic nanoparticle‐based HLA‐peptide‐addressing universal T cell receptor‐engineered T (HAUL TCR‐T) cell therapy in solid tumor

Advances in adoptive cellular therapy for colorectal cancer: a narrative review

Application of adoptive cell therapy in hepatocellular carcinoma

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