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Engineered Cell-Based Therapies: A Vanguard of Design-Driven Medicine

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A Systems Biology Approach to Blood

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 844))

Abstract

Engineered cell-based therapies are uniquely capable of performing sophisticated therapeutic functions in vivo, and this strategy is yielding promising clinical benefits for treating cancer. In this review, we discuss key opportunities and challenges for engineering customized cellular functions using cell-based therapy for cancer as a representative case study. We examine the historical development of chimeric antigen receptor (CAR) therapies as an illustration of the engineering design cycle. We also consider the potential roles that the complementary disciplines of systems biology and synthetic biology may play in realizing safe and effective treatments for a broad range of patients and diseases. In particular, we discuss how systems biology may facilitate both fundamental research and clinical translation, and we describe how the emerging field of synthetic biology is providing novel modalities for building customized cellular functions to overcome existing clinical barriers. Together, these approaches provide a powerful set of conceptual and experimental tools for transforming information into understanding, and for translating understanding into novel therapeutics to establish a newframework for design-driven medicine.

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Abbreviations

APC:

Antigen presenting cell(s)

CAR:

Chimeric antigen receptor(s)

CLL:

Chronic lymphocytic leukemia

CTL:

Cytotoxic T lymphocyte (CTL)

CTLA4:

Cytotoxic T lymphocyte antigen 4

DPLSR:

Discriminant partial least squares regression

EBV:

Epstein-Barr virus

EGFR:

Epidermal growth factor receptor

GVHD:

Graft versus host disease

HLA:

Human leukocyte antigen

IDO:

Indoleamine 2,3-dioxygenase

IL:

Interleukin

iPSC:

Induced pluripotent stem cell(s)

MDSC:

Myeloid derived suppressor cell(s)

MHC:

Major histocompatibility complex

NK:

Natural killer

ODE:

Ordinary differential equation(s)

PCA:

Principal component analysis

PD1:

Programmed cell death protein 1

PDE:

Partial differential equation(s)

scFv:

Single chain variable fragment

STAT3:

Signal transducer and activator of transcription 3

TAA:

Tumor associated antigen(s)

Th1:

Helper T cell, type 1

Th2:

Helper T cell, type 2

TIL:

Tumor infiltrating lymphocyte(s)

TCR:

T cell receptor(s)

TNP:

2,4,6-trinotrophenol

Treg:

Regulatory T cell

VH:

Variable heavy chain

VL:

Variable light chain

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Acknowledgments

RMD and JNL received support from the DefenseAdvanced Research Projects Agency, Award number W911NF-11-2-0066.

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Authors and Affiliations

  1. Northwestern University, 2145 Sheridan Road, Technological Institute, Rm. E136, Evanston, IL, 60208-3120, USA

    Rachel M. Dudek, Yishan Chuang & Joshua N. Leonard

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  1. Rachel M. Dudek
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  2. Yishan Chuang
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  3. Joshua N. Leonard
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Correspondence to Joshua N. Leonard .

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Editors and Affiliations

  1. Departments of Pediatrics and Cell & Molecular Biology, Northwestern University Feinberg School of Medicine and Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA

    Seth Joel Corey

  2. Department of Statistics, Rice University, Houston, Texas, USA

    Marek Kimmel

  3. Northwestern University Comprehensive Cancer Center, Evanston, Illinois, USA

    Joshua N. Leonard

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Dudek, R., Chuang, Y., Leonard, J. (2014). Engineered Cell-Based Therapies: A Vanguard of Design-Driven Medicine. In: Corey, S., Kimmel, M., Leonard, J. (eds) A Systems Biology Approach to Blood. Advances in Experimental Medicine and Biology, vol 844. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2095-2_18

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