Abstract

Adoptive T cell therapy (ACT) is getting acknowledged as the Advanced Therapy Medicinal Products (ATMPs) in many countries and it has evolved as one of the newest regimens to treat cancer. Developed gradually by the basic understanding of cells, involved in innate and adaptive immunity, ACT has emerged as one of the successful immunotherapies in recent times. It broadly includes various cell types such as stem cells, T cells, dendritic cells and Natural Killer cells. By the applications of genetic engineering and advanced cell culture techniques, these cells from patients’ blood, can be manipulated to train them for better efficacy against specific tumor cells. However, only some cells’ subsets have shown promising regression for certain cancer cells types. To understand the reason behind this, technical knowledge about the tumor antigens presentation, tumor microenvironment (TME), hosts’ immune responses and possible issues in the manufacturing of adoptive cellular material for infusion in patients are being explored further. This chapter brings together development of immune cells from basic research to clinical use, newer approaches which have been taken to address the resistance of ACT and future promises of this therapy.

Highlights

  • Human body has a natural tendency to fight against diseases including cancer, aided by its immune system

  • The European Union (EU), governs the regulation of all medicinal products for human use, including advanced therapy medicinal products (ATMPs), i.e., medicinal products comprised of cells, genes, or tissues to ensure the quality, safety, and efficacy of medicines placed on the market in the EU

  • To further improve efficacy of Chimeric Antigen Receptors (CARs), small sized antibodies or nanobodies are recommended to be used with CAR T cell preparation for infusion

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Summary

Introduction

Human body has a natural tendency to fight against diseases including cancer, aided by its immune system. Numbers of approaches have been developed to treat cancer cells using immune-based technology broadly known as cancer immunotherapy (Figure 1 and Table 1). The immune cells play a key role in adoptive cell therapy (ACT) This is achieved by either expanding the autologous cancer-cognate lymphocytes or empowering them by genetic modifications. Cancer treatments by general immunotherapy have their own limitations due to personal variation in the immune response. In such cases, precision medicine through adoptively modified cellular transfers is being preferred lately. The cells to be transferred may be autologous (self-derived) or allogeneic (donor derived) depending upon the availability These cells undergo various genetic modifications to suit the cancer types.

Emergence of ACT
Tumor infiltrating lymphocytes (TILs)
Genetic manipulations of T cells
TCR T cell therapy
CAR T cell therapy
Opportunities and challenges
Tumor regression
Cell selection
Tumor microenvironment
Manufacturing
Delivery system
Regulatory guidelines and cost
Advantages
Enhancing efficacy of ACT
Measuring effectiveness
Countering loss of antigen on cancer cells
Formation of synapse
CARs expressing Heparanase
Minimizing toxicities
Findings
Conclusions
Full Text
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