Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.

Anke Redeker,Ramon Arens

doi:10.3389/fimmu.2016.00345

Abstract

Adoptive cellular therapy (ACT) is a form of immunotherapy whereby antigen-specific T cells are isolated or engineered, expanded ex vivo, and transferred back to patients. Clinical benefit after ACT has been obtained in treatment of infection, various hematological malignancies, and some solid tumors; however, due to poor functionality and persistence of the transferred T cells, the efficacy of ACT in the treatment of most solid tumors is often marginal. Hence, much effort is undertaken to improve T cell function and persistence in ACT and significant progress is being made. Herein, we will review strategies to improve ACT success rates in the treatment of cancer and infection. We will deliberate on the most favorable phenotype for the tumor-specific T cells that are infused into patients and on how to obtain T cells bearing this phenotype by applying novel ex vivo culture methods. Moreover, we will discuss T cell function and persistence after transfer into patients and how these factors can be manipulated by means of providing costimulatory signals, cytokines, blocking antibodies to inhibitory molecules, and vaccination. Incorporation of these T cell stimulation strategies and combinations of the different treatment modalities are likely to improve clinical response rates further.

Highlights

During the recent years, immunotherapy has emerged to be a powerful and potentially curative therapy for the treatment of various types of cancer and recurrent viral diseases
The superior efficacy obtained with Adoptive cellular therapy (ACT) in the treatment of viral infections and virus-associated malignancies compared to the treatment of most solid cancers can be attributed to several factors, including tolerance to tumor-associated antigens (TAAs) and inhibition of tumor-specific T cells due to the suppressive
In a study wherein mice were challenged with B16F10 melanoma, treatment by adoptive transfer of transgenic tumor-specific CD8+ T cells, combined administration of IL-21 and IL-2 and vaccination resulted in higher absolute numbers of circulating tumor-specific T cells and improved tumor-free survival compared to therapy with IL-2 or IL-21 alone [203]

Summary

Introduction

Immunotherapy has emerged to be a powerful and potentially curative therapy for the treatment of various types of cancer and recurrent viral diseases. In preclinical models of ACT, agonistic CD40 antibodies promote tumor-specific T cell expansion and enhanced antitumor activity [155, 156].

Results

Conclusion