eferences 365reactivity, or they may be genetically modified to express disease-targeting
receptors prior to expansion and reinfusion
Chimeric antigen receptor (CAR) A class of membrane-bound fusion proteins
that redirect T-cell specificity toward specified target antigens. First-generation
CARs consist of four major domains: an extracellular single-chain variable
fragment (scFv) that determines target specificity, an extracellular spacer typi-
cally derived from immunoglobulin molecules, a transmembrane domain, and
the cytoplasmic signaling domain of the CD3ζ chain that triggers T-cell activa-
tion upon ligand binding to the scFv. Second- and third-generation CARs con-
tain one or two additional cytoplasmic costimulatory domains, respectively,
that enhance T-cell activation. The most commonly used costimulatory
domains are CD28 and 4-1BB
Suicide gene Genes encoding for protein products that lead to cell death either
directly (e.g., by triggering the apoptosis pathway) or indirectly (e.g., by pro-
cessing prodrugs to lethal products through enzymatic reactions)
References
1 Lienert, F., Lohmueller, J.J., Garg, A., and Silver, P.A. (2014) Synthetic biology in
mammalian cells: next generation research tools and therapeutics. Nat. Rev.
Mol. Cell Biol., 15 (2), 95–107.
2 Kojima, R., Aubel, D., and Fussenegger, M. (2016) Toward a world of theranostic
medication: programming biological sentinel systems for therapeutic
intervention. Adv. Drug Delivery Rev., 105 (Pt A), 66–76.
3 Dudek, R.M., Chuang, Y., and Leonard, J.N. (2014) Engineered Cell-Based
Therapies: A Vanguard of Design-Driven Medicine, Springer, New York,
pp. 369–391.
4 Fischbach, M.A., Bluestone, J.A., and Lim, W.A. (2013) Cell-based therapeutics:
the next pillar of medicine. Sci. Transl. Med., 5 (179), 179ps7.
5 Adams, G.P. and Weiner, L.M. (2005) Monoclonal antibody therapy of cancer.
Nat. Biotechnol., 23 (9), 1147–1157.
6 Hudis, C.A. (2007) Trastuzumab – mechanism of action and use in clinical
practice. N. Engl. J. Med., 357 (1), 39–51.
7 Genentech (1978) First Successful Laboratory Production of Human Insulin
Announced.
8 Egrie, J.C., Strickland, T.W., Lane, J. et al. (1986) Characterization and biological
effects of recombinant human erythropoietin. Immunobiology, 172 (3–5),
213–224.
9 Cancer Facts & Figures (2016). Atlanta: American Cancer Society.
10 Johnson, D.R. and O’Neill, B.P. (2012) Glioblastoma survival in the United States
before and during the temozolomide era. J. Neuro-Oncol., 107 (2), 359–364.
11 Patil, C.G., Yi, A., Elramsisy, A. et al. (2012) Prognosis of patients with multifocal
glioblastoma: a case–control study. J. Neurosurg., 117 (4), 705–711.
12 Greenman, C., Stephens, P., Smith, R. et al. (2007) Patterns of somatic mutation
in human cancer genomes. Nature, 446 (7132), 153–158.