The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies

Sep 24, 2026

Uploaded by Ben

Immunotherapy has transformed cancer treatment, especially approaches that depend on ex vivo expansion of immune cells such as T cells. Despite this progress, barriers persist, including immune cell access problems and the immunosuppressive tumor microenvironment, alongside high treatment cost and inconsistent clinical benefit. This review summarizes literature and trial evidence on cellular immunotherapy strategies, highlighting newer ex vivo modalities and prognostic value of circulating tumor cells.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Adoptive cell therapy and ex vivo expansion

Limitations addressed by newer strategies

Methods

Literature search approach

Clinical trials and guidelines

Results

Tumor infiltrating lymphocyte, CAR, and TCR-modified T cells

Antibody-armed T cells and bispecific approaches

Dendritic cells and natural killer cell strategies

Circulating tumor cells as prognostic markers

Conclusion

The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies Katelyn R. Einloth1 ID , Scott Gayfield1, Thomas McMaster1, Alexander Didier1, Lance Dworkin1, Justin Fortune Creeden2,3* ID 1Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA 2Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA 3Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA Article Info Article Type: Review Article History: Received: 26 August 2022 Revised: 11 Apr. 2023 Accepted: 26 Apr. 2023 ePublished: 29 July 2023 Keywords: Ex vivo expansion Cancer immunotherapy Adoptive cell therapy DC vaccination T cell immunotherapy Circulating tumor cells Abstract Introduction: Immunotherapy has revolutionized how cancer is treated. Many of these immunotherapies rely on ex vivo expansion of immune cells, classically T cells. Still, several immunological obstacles remain, including tumor impermeability by immune cells and the immunosuppressive nature of the tumor microenvironment (TME) . Logistically, high costs of treatment and variable clinical responses have also plagued traditional T cell-based immunotherapies. Methods: To review the existing literature on cellular immunotherapy, the PubMed database was searched for publications using variations of the phrases “cancer immunotherapy”, “ex vivo expansion”, and “adoptive cell therapy”. The [Clinicaltrials.gov](Clinicaltrials.gov) database was searched for clinical trials related to ex vivo cellular therapies using the same phrases. The National Comprehensive Cancer Network guidelines for cancer treatment were also referenced. Results: To circumvent the challenges of traditional T cell-based immunotherapies, researchers have developed newer therapies including tumor infiltrating lymphocyte (TIL), chimeric antigen receptor (CAR), T cell receptor (TCR) modified T cell, and antibody-armed T cell therapies. Additionally, newer immunotherapeutic strategies have used other immune cells, including natural killer (NK) and dendritic cells (DC), to modulate the T cell immune response to cancers. From a prognostic perspective, circulating tumor cells (CTC) have been used to predict cancer morbidity and mortality. Conclusion: This review highlights the mechanism and clinical utility of various types of ex vivo cellular therapies in the treatment of cancer. Comparing these therapies or using them in combination may lead to more individualized and less toxic chemotherapeutics. Introduction Globally, one in five men and one in six women will be diagnosed with cancer in their lifetime.1 Depending on the type and stage of cancer, treatments may target specific portions of the body, known as local therapy, or may affect the entire body, known as systemic therapy. Examples of local therapy include surgery and radiation therapy, while drug treatments such as chemotherapy and immunotherapy are examples of systemic treatments.2 Of these, systemic immunotherapeutic interventions are most productively enhanced by ex vivo (i.e., outside the body) laboratory techniques that allow for the expansion of therapeutic or prognostic biological material. Adoptive cell therapy (ACT) is perhaps the most widely recognized type of immunotherapy relying on ex vivo cellular preparation. ACT requires ex vivo modification and expansion of autologous cells before these cells are infused back into the patient.3 The earliest forms of ACT used T cells to treat cancers. Today, there are multiple typesofT cell therapy, including tumor infiltrating lymphocyte (TIL) therapy, chimeric antigen receptor (CAR) therapy, T cell receptor (TCR) modified T cell therapy, and therapies combining T cells with antibodies against specific tumor markers. Recent studies involving CAR-T cell therapy *Corresponding author: Justin F. Cree

FAQs

What challenges limit traditional T cell-based ex vivo immunotherapies?

Key obstacles include limited tumor access by immune cells and the immunosuppressive tumor microenvironment. High costs and variable clinical responses also hinder broader success.

Which newer ex vivo immune cell therapies are discussed in the review?

The review highlights tumor infiltrating lymphocyte (TIL) therapy, CAR-T cells, TCR-modified T cells, antibody-armed T cells, and bispecific antibody-armed T cell strategies.

How are circulating tumor cells (CTCs) used for prognosis?

CTCs can be expanded ex vivo to identify tumor-specific biomarkers and predict survival outcomes. Research focuses on efficient isolation and optimized culture conditions to support these uses.

Sep 24, 2026

Uploaded by Ben