Adopting tomorrow’s therapies today: a perspective review of adoptive cell therapy in lung cancer - review

Sep 23, 2026

Uploaded by Liam

Lung cancer remains a major global health challenge and a leading cause of cancer-related death, despite advances from targeted therapy and immune checkpoint inhibitors (ICIs). For patients who fail to respond or develop resistance to ICIs, adoptive cell therapy (ACT) is being explored to strengthen antitumor immunity. ACT uses patient-derived T cells from tumors or peripheral blood, including CAR-T, engineered TCR therapies, and tumor-infiltrating lymphocytes. This review summarizes major ACT subtypes, lung-cancer evidence, limitations, risks and benefits, and future perspectives, including T cell engagers, mRNA vaccine approaches, and combination strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Plain language summary

Keywords

Introduction

Lung cancer burden and unmet needs

Adoptive cell therapy overview

Cellular immunotherapy concept

Mechanisms and clinical rationale

TherapeuTic advances in Medical Oncology Review Adopting tomorrow’s therapies today: a perspective review of adoptive cell therapy in lung cancer Faith Abodunrin, Daniel J Olson, Oluwatosin Emehinola and Christine M Bestvina Abstract: Lung cancer is the leading cause of all cancer-related deaths in the United States and remains a global health challenge. While targeted therapy has revolutionized the treatment landscape of nonsmall cell lung cancer, many patients lack actionable mutations. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), have significantly impacted outcomes in lung cancer in the last decade. Some patients, however, never respond or become refractory to ICIs. Newer therapies aimed at augmenting the immune system and enhancing antitumor effects are currently being explored. Adoptive cell therapy (ACT) employs T cells isolated from either tumors or peripheral blood and often engineers them to effect antitumor immune response. Chimeric antigen receptor T (CAR-T) cell therapy, engineered T cell receptor therapy, and tumor-infiltrating lymphocytes are examples of adoptive cellular therapies. CAR-T cell therapy has been successful in the treatment of hematological malignancies with several CAR products gaining approval in the treatment of refractory blood cancers. The success of ACTs in hematological cancers has fueled research into the role of these therapies in solid cancers including lung cancer. Many trials have had early promising results, with many clinical trials currently enrolling. There are many limitations to the efficacy of ACTs, as well as risks and benefits with the individual subtypes of ACT. With growing knowledge about tumor antigens and more advanced cell engineering, there is potential for ACT to result in durable responses in immunologically “cold” tumors. Here, we review the major subtypes of ACTs, evidence supporting their use in lung cancer, challenges, and future perspectives in ACTs. Additionally, we include T cell engagers and mRNA vaccine studies and potential combinatorial strategies in lung cancer. Plain language summary Adopting tomorrow’s therapies today: a perspective review of immune cell therapies and mRNA vaccines targeting lung cancer cells Lung cancer is a prominent cause of cancer-related deaths in the United States and worldwide. Several approaches to treat lung cancer has been used over the years. We know that the immune system is not only designed to fight infections but also to recognize and kill cancer cells. A group of immune cells called killer T cells can bind to markers on the surface of cancerous cells. The understanding of the role the immune system plays in attacking cancer cells led to the development of immunotherapy. Immune checkpoint inhibitors are drugs that target proteins that act as “off-switches” in the immune system. Outcomes in lung cancer have improved with the introduction of immune checkpoint inhibitors, but still only a minority of patients have long term benefit. A new type of immunotherapy called adoptive cell therapy (ACT) is the focus of this perspective review. ACT is also referred to as cellular immunotherapy. This is an umbrella term including treatment that uses the cells of the immune system to get rid of cancer. There are different ways of utilizing ACT TherAdv Med Oncol 2025, Vol. 17: 1–18 DOI: 10. 1177/ 17588359251320280 © The Author(s), 2025. Article reuse guidelines: [sagepub.com/journals](sagepub.com/journals)permissions Correspondence to: Christine M Bestvina Section of Hematology and Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637, USA cbestvina@bsd.uchicago. edu Faith Abodunrin Daniel J Olson Section of Hematology and Oncology, Department of Medicine, The University of Chicago Medicine, Chicago, IL, USA Oluwatosin Emehinola Department of Internal Medicine, New York Medical College at Saint Michael’s Medical Center, Newark

FAQs

What problem does this review address in lung cancer treatment?

It addresses the persistent challenge of poor outcomes in lung cancer, especially for patients who do not respond to or become refractory to immune checkpoint inhibitors.

What is adoptive cell therapy (ACT) and how is it implemented?

ACT is a form of cellular immunotherapy that uses immune cells—often patient T cells—isolated and sometimes genetically engineered or modified to enhance antitumor activity.

Which ACT subtypes and related approaches are discussed?

The review covers major ACT subtypes such as CAR-T cell therapy, engineered TCR therapy, and tumor-infiltrating lymphocytes, and it also includes T cell engagers, mRNA vaccine studies, and potential combination strategies.

Sep 23, 2026

Uploaded by Liam