Promises and challenges of adoptive T-cell therapies for solid tumours

Paper

Abstract

Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas-cancer genomics, cancer immunology and cell-therapy manufacturing-that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.

Analysis

Paper intelligence

Summary

Adoptive T-cell therapy, including CAR-T, shows promise for solid tumors by leveraging advances in genomics, immunology, and manufacturing, despite significant challenges.

Key findings

Adoptive T-cell therapy can lead to durable responses and cure in some cancer patients.
Technological advances are enabling personalized T-cell therapies for cancer.
Understanding intratumor heterogeneity and neoantigens is crucial for solid tumor treatment.
Strategies to overcome T-cell exhaustion and tumor immunosuppression are under development.

Methods

Transplant of tumor-infiltrating lymphocytes.
Transplant of genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors.

Limitations

Many patients with advanced-stage or high-risk cancers still die due to metastatic disease.
T-cell therapies face many challenges for solid tumor treatment.

Applications

Treatment of advanced-stage or high-risk cancers.
Treatment of solid tumors.

Confidence100%

Discovery

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Source record

Publication metadata

Authors: Matteo Morotti; Ashwag Albukhari; Abdulkhaliq Alsaadi; Mara Artibani; James D. Brenton; Stuart M. Curbishley; Tao Dong; Michael L. Dustin; Zhiyuan Hu; Nicholas McGranahan; Martin L. Miller; Laura Santana-Gonzalez; Leonard W. Seymour; Tingyan Shi; Peter Van Loo; Christopher Yau; Helen White; Nina Wietek; David N. Church; David C. Wedge; Ahmed A. Ahmed
Published: Mar 29, 2021
Journal or venue: British Journal of Cancer
DOI: 10.1038/s41416-021-01353-6
Paper type: journal article
Source: Openalex

DOI OpenAlex