Facing the future: challenges and opportunities in adoptive T cell therapy in cancer

ABSTRACT

Introduction: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain.

Areas covered: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed.

Expert opinion: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. The heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.

KEYWORDS:

• T cells
• T cell immunotherapy
• adoptive cell therapy
• solid tumors
• cancer

Article highlights

• An overview of the T cell ACT field is here presented from a development, strategy, and production perspective. Antigen targeting strategies, key aspects and choices in the manufacturing process, and tumor evasion strategies are explored.

• Different targeting strategies and well-known therapies adopting these strategies are presented and contrasted against each other, including TIL therapy, CAR T cell therapy, transgenic TCR therapy, and neoantigen-based therapy.

• Important aspects of T cell ACT production, such as cytokine use in the culturing protocols, and the choice of culture system are explored.

• An overview of relevant tumor evasion mechanisms is presented in order to visualize the obstacles to successful T cell ACT.

• The conclusions drawn from the knowledge summarized in this review point toward the need of multi-pronged approaches to optimize the therapeutic success of T cell ACT. The choice of target and production methods are central to the patient outcome, but additional therapies targeting tumor evasion mechanisms and the microenvironment, including suppressive immune cells, might be necessary to extend the efficacy of this type of treatment.

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Acknowledgments

The figures were prepared using elements from the Motifolio collection.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers’ disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.