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54 Aoife M. Brennan et al.
rapidly destroyed by the immune system prior to establishing colonization, leading to
variable delivery. A further disadvantage is a potential for systemic cytokine release
and infection with replication-competent organisms.
These limitations may be overcome with further development of our synthetic biology toolbox, as discussed previously. These tools have been used to engineer bacterial
cells to achieve enhanced tumor targeting [17,146–148]. One approach to enhance
tumor targeting is to display a protein such as an antibody on the bacterial cell surface
that binds to epitopes on tumor cells. The display of histone-like protein A (HlpA) from
Streptococcus on E. coli Nissle demonstrated notable binding to colorectal tumor cells
where HlpA binds to upregulated tumor surface HSPG [83] . Synthetic nanobody-based
adhesins have been developed and surface-displayed on E. coli Nissle and have demonstrated tumor colonization with a significantly lower dosage as well as lower retention in
healthy organs in animal models [147]. These advances may lead to the ability to consistently colonize GI-associated tumors or liver metastasis following oral administration.
Preventing infection with the engineered microbe is important, particularly for
approaches that require systemic delivery. Auxotrophic gene knockouts such as thyA
and dapA have been engineered into bacterial cells and have not only prevented growth
outside of the TME but also limited growth inside solid tumors [63]. In certain situations,
controlled growth within the tumor is desirable, and the ideal auxotroph or kill switch
would allow controlled replication with the tumor but limit replication in healthy tissue
and the environment. Addressing this particular challenge is an area of ongoing
development.
Ultimately, the design of an engineered bacterial therapeutic for cancer is multifactorial, incorporating chassis selection, effector function, safety, and patient considerations, including the route of administration.
5. Regulatory considerations in the development of engineered
bacteria as therapeutics
Delivering on the therapeutic potential of engineered bacteria requires the translation of the preclinical data accumulated in animal models into the clinic and the initiation of human clinical trials. This process requires the approval of relevant national
authorities as well as ethics committees. As with other therapeutic products, approval,
and licensure requires the demonstration of safety, efficacy (from well-controlled clinical
trials), and quality i.e., reliability, robustness, and consistency of each batch produced
(ICH M4 Guidelines).
Bacterial therapeutics are classified as LBPs and genetically modified bacteria are classified as recombinant LBPs. In the United States, recombinant LBPs are regulated by the
FDA through the Center for Biologics Evaluation and Research. In 2016, the FDA
issued a guidance document describing the regulatory considerations for conducting
clinical trials with LBPs [82]. More recently, the European Pharmacopeia published a
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monograph setting the quality standards for LBPs for human use, effective in April
2019 [149].
The first step in the clinical evaluation of any potential therapeutic product is the clinical trial application or investigational new drug (IND) application. Consultation prior to
submission of the application to initiate clinical trials and regularly throughout development is critical in this new area, as minimal precedents exist and current regulatory guidance includes general considerations only. Each LBP contains unique properties,
including the route of administration, pathogenicity potential, colonization, clearance,
microbial products, and other factors that influence the data required to support the
benefit-risk evaluation by regulators. For example, bacterial components such as lipopolysaccharides will result in different risks for an oral product compared to a product
that is intended to be administered intravenously or intratumorally. Among the most
important safety risks to consider when assembling the clinical trial application or
IND is the potential for infection with the engineered organism, which may be
influenced by the biodistribution of the product. Preclinical distribution studies following administration that are representative of the intended clinical route may be required
to support a clinical trial. Demonstrating sensitivity to commonly prescribed antibiotics is
also important to guide the treatment of potential infections in the clinic.
In common with all investigational medicinal products, the manufacturing facility
where the engineered microbe is manufactured should operate under Good Manufacturing Practices. A number of unique manufacturing considerations do apply when preparing to conduct a clinical trial with engineered bacteria, which include the following:
• The genetic sequence of exogenously introduced genes, including a high-quality, com-
plete genome sequence for the engineered clinical candidate strain will be required.
• Evidence supporting the stability of strain modifications over time, particularly during
fermentation, should be considered.
• The ability of the organism to replicate or persist in the environment should be
described along with any biocontainment strategies incorporated into the engineering.
• Assays to determine the absence of contamination from adventitious agents are
required to be developed, which may be challenging with an LBP. The required sen-
sitivity (particularly for products intended for nonoral routes of administration) often
requires culture-based methodology.
Following completion of the IND process in the United States, regional ethics committees
or institutional review boards will review the clinical protocol and other study documents.
Because engineered bacteria are considered biological agents, reviews by institutional
biosafety committees are also frequently required. The purpose of this committee is to
assess the environmental risk of the product and the ability of the engineered bacteria
to survive and replicate in the environment as well as any potential toxicity should an
unintended person be exposed. This environmental review differs globally, thus the process must be understood for the specific region in which the clinical trial will take place.
55Engineered microbes for cancer immunotherapy
56 Aoife M. Brennan et al.
6. Conclusion
The field of cancer immunotherapy started with the injection of pathogenic bacteria intratumorally, but the broad adoption of bacteria in cancer therapeutics has historically been limited by difficulty finding a balance between efficacy and safety. Synthetic
biology now provides tools to precisely engineer bacteria to address some of these historical limitations and multiple academic groups and biotech companies are actively pursuing this area of research. Ongoing clinical programs will provide important learnings
from trials that include engineered strains with different chassis organisms, route of
administration, and genetic modifications across a range of indications. The current confluence of advancing synthetic biology tools, greater understanding of the
immunobiology of cancer, the potential of bacteria to address multiple mechanisms
simultaneously as well as a regulatory pathway that is developing sets the stage for rapid
advancement in this space to address difficult cancers in patients.
References
[1] Chang AH, Parsonnet J. Role of bacteria in oncogenesis. Clin Microbiol Rev 2010;23(4):837–57.
[2] Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-
specific intracellular bacteria. Science 2020;368(6494):973 – 80.
[3] Larsen ES, Joensen UN, Poulsen AM, et al. Bacillus Calmette–Guerin immunotherapy for bladder
cancer: a review of immunological aspects, clinical effects and BCG infections. APMIS
2020;128:92–103.
[4] Ebbell B, Banov L. The papyrus Ebers: the greatest Egyptian medical document. Copenhagen, Den-
mark, Levin: Munksgaard; 1937.
[5] Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of
ten original cases. 1893. Clin Orthop Relat Res 1991;262:3–11.
[6] Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun
2020;11:3801.
[7] TICE
[8] Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of super-
[9] Redelman-Sidi G, Glickman MS, Bochner BH. The mechanism of action of BCG therapy for bladder
[10] Perez-Jacoiste Ası´n MA, Ferna´ndez-Ruiz M, Lo´pez-Medrano F, et al. Bacillus Calmette-Guerin
[11] Cernuschi T, Malvolti S, Nickels E, et al. Bacillus Calmette-Guerin (BCG) vaccine: a global assess-
[12] Danino T, Lo J, Prindle A, et al. In vivo gene expression dynamics of tumor-targeted bacteria. ACS
[13] Felgner S, Kocijancic D, Frahm M, Weiss S. Bacteria in cancer therapy: renaissance of an old concept.
[14] Ganai S, Arenas RB, Sauer JP. In tumors Salmonella migrate away from vasculature toward the tran-
[15] Kocijancic D, Felgner S, Frahm M, et al. Therapy of solid tumors using probiotic Symbioflor-2:
®
. BCG United States Prescribing Information. Merck & Co., Inc.; 2020. March.
ficial bladder tumors. J Urol 1976;116(2):180–3.
cancer – a current perspective. Nat Rev Urol 2014;11(3):153–62.
(BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer:
incidence, risk factors, and outcome in a single-institution series and review of the literature. Medicine
(Baltimore) 2014;93(17):236–54.
ment of demand and supply balance. Vaccine 2018;36(4):498–506.
Synth Biol 2012;1:465–70.
Int J Microbiol 2016;2016:8451728.
sition zone and induce apoptosis. Cancer Gene Ther 2011;18:457–66.
restraints and potential. Oncotarget 2016;7(16):22605–22.
[16] Zhao M, Yang M, Li XM, et al. Tumor-targeting bacterial therapy with amino acid auxotrophs of
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci U S A 2005;102(3):755–60.
[17] Zhou S, Gravekamp C, Bermudes D, Liu K. Tumour-targeting bacteria engineered to fight cancer.
Nat Rev Cancer 2018;18(12):727–43.
[18] Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin
Microbiol Rev 2009;22(2):240–73.
[19] Aglietti RA, Dueber EC. Recent insights into the molecular mechanisms underlying pyroptosis and
gasdermin family functions. Trends Immunol 2017;38(4):261–71.
[20] Xia X, Wang X, Cheng Z, et al. The role of pyroptosis in cancer: pro-cancer or pro-“host”? Cell
Death Dis 2019;10:650.
[21] Westphal K, Leschner S, Jablonska J, et al. Containment of tumor-colonizing bacteria by host neu-
trophils. Cancer Res 2008;68:2952–60.
[22] Lee CH, Lin ST, Liu JJ, et al. Salmonella induce autophagy in melanoma by the downregulation of
AKT/mTOR pathway. Gene Ther 2014;21:309–16.
[23] Uchugonova A, Zhang Y, Salz R, et al. Imaging the different mechanisms of prostate cancer cell-
killing by tumor-targeting Salmonella typhimurium A1-R. Anticancer Res 2015;35:5225–9.
[24] Zhou S, Zhao Z, Lin Y, et al. Suppression of pancreatic ductal adenocarcinoma growth by
intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system. Cancer Biol Ther 2016;17:732–40.
[25] Saccheri F, Pozzi C, Avogadri F, et al. Bacteria-induced gap junctions in tumors favor antigen cross-
presentation and antitumor immunity. Sci Transl Med 2010;2(44), 44ra57.
[26] Kim JE, Phan TX, Nguyen VH, et al. Salmonella typhimurium suppresses tumor growth via the pro-
inflammatory cytokine interleukin-1beta. Theranostics 2015;5(12):1328–42.
[27] Nguyen CT, Hong SH, Sin JI, et al. Flagellin enhances tumor-specific CD8
+
T cell immune responses
through TLR5 stimulation in a therapeutic cancer vaccine model. Vaccine 2013;31(37):3879–87.
[28] Phan TX, Nguyen VH, Duong MT, et al. Activation of inflammasome by attenuated Salmonella typ-
himurium in bacteria-mediated cancer therapy. Microbiol Immunol 2015;59(11):664–75.
[29] Leigh ND, Bian G, Ding X, et al. A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic
lymphocyte-mediated tumor immunity. PLoS One 2014;9(1), e85587.
[30] Kupz A, Curtiss R, Bedoui S, Strugnell RA. In vivo IFN-gamma secretion by NK cells in response to
Salmonella typhimurium requires NLRC4 inflammasomes. PLoS One 2014;9, e97418.
[31] Low KB, Ittensohn M, Le T, et al. Lipid A mutant Salmonella with suppressed virulence and
TNFalpha induction retain tumor-targeting in vivo. Nat Biotechnol 1999;17(1):37–41.
[32] Jeong JH, Song M, Park SI, et al. Salmonella enterica serovar gallinarum requires ppGpp for internal-
ization and survival in animal cells. J Bacteriol 2008;190:6340–50.
[33] Bettegowda C, Huang X, Lin J, et al. The genome and transcriptomes of the anti-tumor agent Clos-
tridium novyi-NT. Nat Biotechnol 2006;24(12):1573–80.
[34] Chagnon A, Hudon C, McSween G, et al. Cytotoxicity and reduction of animal cell growth by Clos-
tridium M-55 spores and their extracts. Cancer 1972;29:431–4.
[35] Middlebrook JL, Dorland RB. Bacterial toxins: cellular mechanisms of action. Microbiol Rev
1984;48:199–221.
[36] Agrawal N, Bettegowda C, Cheong I, et al. Bacteriolytic therapy can generate a potent immune
response against experimental tumors. Proc Natl Acad Sci U S A 2004;101(42):15172–7.
[37] Dang LH, Bettegowda C, Huso DL, et al. Combination bacteriolytic therapy for the treatment of
experimental tumors. Proc Natl Acad Sci U S A 2001;98(26):15155–60.
[38] Chandra D, Jahangir A, Quispe-Tintaya W, et al. Myeloid-derived suppressor cells have a central role
in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young
and old mice. Br J Cancer 2013;108:2281–90.
[39] Quispe-Tintaya W, Chandra D, Jahangir A, et al. Nontoxic radioactive Listeria(at) is a highly effective
therapy against metastatic pancreatic cancer. Proc Natl Acad Sci U S A 2013;110(21):8668–73.
[40] Jahangir A, Chandra D, Quispe-Tintaya W, et al. Immunotherapy with Listeria reduces metastatic
breast cancer in young and old mice through different mechanisms. Onco Targets Ther 2017;6(9),
e1342025.
[41] Kim SH, Castro F, Paterson Y, Gravekamp C. High efficacy of a Listeria-based vaccine against met-
astatic breast cancer reveals a dual mode of action. Cancer Res 2009;69:5860–6.
57Engineered microbes for cancer immunotherapy
58 Aoife M. Brennan et al.
[42] Freitag NE, Rong L, Portnoy DA. Regulation of the prfA transcriptional activator of Listeria mono-
cytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. Infect
Immun 1993;61:2537–44.
[43] Wood LM, Paterson Y. Attenuated Listeria monocytogenes: a powerful and versatile vector for the future
of tumor immunotherapy. Front Cell Infect Microbiol 2014;4:51.
[44] Agarwal N, Sonpavde G, Sternberg CN. Novel molecular targets for the therapy of castration-resistant
prostate cancer. Eur Urol 2012;61(5):950–60.
[45] Thompson RJ, Bouwer HG, Portnoy DA, Frankel FR. Pathogenicity and immunogenicity of a
Listeria monocytogenes strain that requires D-alanine for growth. Infect Immun 1998;66:3552–61.
[46] Roberts NJ, Zhang L, Janku F, et al. Intratumoral injection of Clostridium novyi-NT spores induces
antitumor responses. Sci Transl Med 2014;6(249), 249ra111.
[47] Toso JF, Gill VJ, Hwu P, et al. Phase I study of the intravenous administration of attenuated Salmonella
typhimurium to patients with metastatic melanoma. J Clin Oncol 2002;20:142–52.
[48] Cameron DE, Bashor CJ, Collins JJ. A brief history of synthetic biology. Nat Rev Microbiol 2014;12
(5):381–90.
[49] Caliendo F, Dukhinova M, Siciliano V. Engineered cell-based therapeutics: synthetic biology meets
immunology. Front Bioeng Biotechnol 2019;7:43.
[50] Mathur M, Xiang JS, Smolke CD. Mammalian synthetic biology for studying the cell. J Cell Biol
2017;216(1):73–82.
[51] Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol
1961;3:318–56.
[52] Jacob F, Monod J. On the regulation of gene activity. Cold Spring Harb Symp Quant Biol
1961;26:193–211.
[53] Benner SA. Synthetic biology: act natural. Nature 2003;421(6919):118.
[54] Salis HM, Mirsky EA, Voigt CA. Automated design of synthetic ribosome binding sites to control
protein expression. Nat Biotechnol 2009;27(10):946–50.
[55] Brophy JA, Voigt CA. Principles of genetic circuit design. Nat Methods 2014;11(5):508–20.
[56] Chien T, Doshi A, Danino T. Advances in bacterial cancer therapies using synthetic biology. Curr
Opin Syst Biol 2017;5:1–8.
[57] Siuti P, Yazbek J, Lu TK. Synthetic circuits integrating logic and memory in living cells. Nat Bio-
technol 2013;31(5):448–52.
[58] Claesen J, Fischbach MA. Synthetic microbes as drug delivery systems. ACS Synth Biol 2015;4
(4):358–64.
[59] Charbonneau MR, Isabella VM, Li N, Kurtz CB. Developing a new class of engineered live bacterial
therapeutics to treat human diseases. Nat Commun 2020;11(1):1738.
[60] Pedrolli DB, Ribeiro NV, Squizato PN, et al. Engineering microbial living therapeutics: the synthetic
biology toolbox. Trends Biotechnol 2019;37(1):100–15.
[61] Isabella VM, Ha BN, Castillo MJ, et al. Development of a synthetic live bacterial therapeutic for the
human metabolic disease phenylketonuria. Nat Biotechnol 2018;36:857.
[62] Kurtz CB, Millet YA, Puurunen MK, et al. An engineered E. coli Nissle improves hyperammonemia
and survival in mice and shows dose-dependent exposure in healthy humans. Sci Transl Med 2019;11
(475), eaau7975.
[63] Leventhal DS, Sokolovska A, Li N, et al. Immunotherapy with engineered bacteria by targeting the
STING pathway for anti-tumor immunity. Nat Commun 2020;11(1):2739.
[64] Riglar DT, Giessen TW, Baym M, et al. Engineered bacteria can function in the mammalian gut long-
term as live diagnostics of inflammation. Nat Biotechnol 2017;35(7):653–8.
[65] Courbet A, Endy D, Renard E, et al. Detection of pathological biomarkers in human clinical samples
via amplifying genetic switches and logic gates. Sci Transl Med 2015;7(289), 289ra83.
[66] Jayaraman P, Holowko MB, Yeoh JW, et al. Repurposing a two-component system-based biosensor
for the killing of Vibrio cholerae. ACS Synth Biol 2017;6(7):1403–15.
[67] Mao N, Cubillos-Ruiz A, Cameron DE, Collins JJ. Probiotic strains detect and suppress cholera in
mice. Sci Transl Med 2018;10(445), eaao2586.
[68] Gardner TS, Cantor CR, Collins JJ. Construction of a genetic toggle switch in Escherichia coli. Nature
2000;403(6767):339–42.
[69] Kotula JW, Kerns SJ, Shaket LA, et al. Programmable bacteria detect and record an environmental
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
signal in the mammalian gut. Proc Natl Acad Sci U S A 2014;111(13):4838–43.
[70] Mimee M, Tucker AC, Voigt CA, Lu TK. Programming a human commensal bacterium, Bacteroides
thetaiotaomicron, to sense and respond to stimuli in the murine gut microbiota. Cell Syst 2015;1
(1):62–71.
[71] Espah Borujeni A, Channarasappa AS, Salis HM. Translation rate is controlled by coupled trade-offs
between site accessibility, selective RNA unfolding and sliding at upstream standby sites. Nucleic
Acids Res 2014;42(4):2646–59.
[72] Espah Borujeni A, Salis HM. Translation initiation is controlled by RNA folding kinetics via a ribo-
some drafting mechanism. J Am Chem Soc 2016;138(22):7016–23.
[73] Espah Borujeni A, Cetnar D, Farasat I, et al. Precise quantification of translation inhibition by mRNA
structures that overlap with the ribosomal footprint in N-terminal coding sequences. Nucleic Acids
Res 2017;45(9):5437–48.
[74] Sonnenborn U. Escherichia coli strain Nissle 1917-from bench to bedside and back: history of a special
Escherichia coli strain with probiotic properties. FEMS Microbiol Lett 2016;363(19), fnw212.
[75] Shepherd ES, DeLoache WC, Pruss KM, et al. An exclusive metabolic niche enables strain engraft-
ment in the gut microbiota. Nature 2018;557(7705):434–8.
[76] Fujimori M. Genetically engineered bifidobacterium as a drug delivery system for systemic therapy of
metastatic breast cancer patients. Breast Cancer 2006;13(1):27–31.
[77] Hamaji Y, Fujimori M, Sasaki T, et al. Strong enhancement of recombinant cytosine deaminase activ-
ity in Bifidobacterium longum for tumor-targeting enzyme/prodrug therapy. Biosci Biotechnol Biochem 2007;71(4):874–83.
[78] Yazawa K, Fujimori M, Amano J. Bifidobacterium longum as a delivery system for cancer gene therapy:
selective localization and growth in hypoxic tumors. Cancer Gene Ther 2000;7(2):269–74.
[79] Staedtke V, Roberts NJ, Bai RY, Zhou S. Clostridium novyi-NT in cancer therapy. Genes Dis 2016;3
(2):144–52.
[80] van Pijkeren JP, Morrissey D, Monk IR, et al. A novel Listeria monocytogenes-based DNA delivery
system for cancer gene therapy. Hum Gene Ther 2010;21(4):405–16.
[81] Lee JW, Chan CTY, Slomovic S, Collins J. Next-generation biocontainment systems for engineered
organisms. Nat Chem Biol 2018;14(6):530–7.
[82] Food and Drug Administration (United States). Guidance for industry. Early clinical trials with live
biotherapeutic products: chemistry, manufacturing, and control information. June; 2016.
[83] Ho CL, Tan HQ, Chua KJ, et al. Engineered commensal microbes for diet-mediated colorectal-
cancer chemoprevention. Nat Biomed Eng 2018;2(1):27–37.
[84] Hwang IY, Koh E, Wong A, et al. Engineered probiotic Escherichia coli can eliminate and prevent
Pseudomonas aeruginosa gut infection in animal models. Nat Commun 2017;8:15028.
[85] Danino T, Prindle A, Kwong GA, et al. Programmable probiotics for detection of cancer in urine. Sci
Transl Med 2015;7(289), 289ra84.
[86] Steidler L, Neirynck S, Huyghebaert N, et al. Biological containment of genetically modified
Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol 2003;21(7):785
[87] Rovner AJ, Haimovich AD, Katz SR, et al. Recoded organisms engineered to depend on synthetic
amino acids. Nature 2015;518(7537):89–93.
[88] Lajoie MJ, Rovner AJ, Goodman DB, et al. Genomically recoded organisms expand biological func-
tions. Science 2013;342(6156):357–60.
[89] Mandell DJ, Lajoie MJ, Mee MT, et al. Biocontainment of genetically modified organisms by syn-
thetic protein design. Nature 2015;518(7537):55–60.
[90] Marlie`re P, Patrouix J, D€oring V, et al. Chemical evolution of a bacterium’s genome. Angew Chem
Int Ed Engl 2011;50(31):7109–14.
[91] Pinheiro VB, Taylor AI, Cozens C, et al. Synthetic genetic polymers capable of heredity and evolu-
tion. Science 2012;336(6079):341–4.
[92] Gallagher RR, Patel JR, Interiano AL, et al. Multilayered genetic safeguards limit growth of micro-
organisms to defined environments. Nucleic Acids Res 2015;43(3):1945–54.
[93] Huang S, Lee AJ, Tsoi R, et al. Coupling spatial segregation with synthetic circuits to control bacterial
survival. Mol Syst Biol 2016;12(2):859.
–9.
59Engineered microbes for cancer immunotherapy
60 Aoife M. Brennan et al.
[94] Chan CT, Lee JW, Cameron DE, et al. ‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial
containment. Nat Chem Biol 2016;12(2):82–6.
[95] Contreras A, Molin S, Ramos JL. Conditional-suicide containment system for bacteria which min-
eralize aromatics. Appl Environ Microbiol 1991;57(5):1504–8.
[96] Molina L, Ramos C, Ronchel MC, et al. Construction of an efficient biologically contained pseu-
domonas putida strain and its survival in outdoor assays. Appl Environ Microbiol 1998;64(6):2072–8.
[97] Chavez A, Pruitt BW, Tuttle M, et al. Precise Cas9 targeting enables genomic mutation prevention.
Proc Natl Acad Sci U S A 2018;115(14):3669–73.
[98] Callura JM, Dwyer DJ, Isaacs FJ, et al. Tracking, tuning, and terminating microbial physiology using
synthetic riboregulators. Proc Natl Acad Sci U S A 2010;107(36):15898–903.
[99] Janku F, Gounder M, Pezeshki AM, et al. First-in-man clinical trial of intratumoral injection of Clos-
tridium novyi-NT spores in patients with treatment-refractory advanced solid tumors: safety, activity,
and immune response [abstract]. Cancer Immunol Res 2019;7(2 Suppl). Abstract A011.
[100] Le DT, Picozzi VJ, Ko AH, et al. Results from a phase IIb, randomized, multicenter study of GVAX
pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pan-
creatic adenocarcinoma (ECLIPSE study). Clin Cancer Res 2019;25(18):5493–502.
[101] Huh WK, Brady WE, Fracasso PM, et al. Phase II study of axalimogene filolisbac (ADXS-HPV) for
platinum-refractory cervical carcinoma: an NRG oncology/gynecologic oncology group study.
Gynecol Oncol 2020;S0090-8258(20):32317–9.
[102] Wick W, Wick A, Chinot OL, et al. Oral DNA vaccination targeting VEGFR2 combined with anti-
PDL1 avelumab in patients with progressive glioblastoma: safety run-in results—NCT03750071.
J Clin Oncol 2020;38(Suppl). Abstract 3001.
[103] Nakamura T, Sasaki T, Fujimori M, et al. Cloned cytosine deaminase gene expression of
Bifidobacterium longum and application to enzyme/pro-drug therapy of hypoxic solid tumors. Biosci
Biotechnol Biochem 2002;66(11):2362–6.
[104] Theys J, Landuyt W, Nuyts S, et al. Specific targeting of cytosine deaminase to solid tumors by
engineered Clostridium acetobutylicum. Cancer Gene Ther 2001;8(4):294–7.
[105] Triplett TA, Garrison KC, Marshall N, et al. Reversal of indoleamine 2,3-dioxygenase-mediated can-
cer immune suppression by systemic kynurenine depletion with a therapeutic enzyme. Nat Bio-
technol 2018;36(8):758–64.
[106] G€unther J, D€abritz J, Wirthgen E. Limitations and off-target effects of tryptophan-related IDO inhib-
itors in cancer treatment. Front Immunol 2019;10:1801.
[107] West K, Fisher A, Leventhal D, et al. Metabolic modulation of the tumor microenvironment using
Synthetic Biotic™ medicines. Cancer Res 2018;78(13). Abstract 2920.
[108] Jose J. Autodisplay: efficient bacterial surface display of recombinant proteins. Appl Microbiol Bio-
technol 2006;69(6):607–14.
[109] Flentie K, Kocher B, Gammon ST, et al. A bioluminescent transposon reporter-trap identifies tumor-
specific microenvironment-induced promoters in Salmonella for conditional bacterial-based tumor
therapy. Cancer Discov 2012;2(7):624–37.
[110] Jiang SN, Park SH, Lee HJ, et al. Engineering of bacteria for the visualization of targeted delivery of a
cytolytic anticancer agent. Mol Ther 2013;21(11):1985–95.
[111] Ryan RM, Green J, Williams PJ, et al. Bacterial delivery of a novel cytolysin to hypoxic areas of solid
tumors. Gene Ther 2009;16(3):329–39.
[112] St Jean AT, Swofford CA, Panteli JT, et al. Bacterial delivery of
Staphylococcus aureus alpha-hemolysin
causes regression and necrosis in murine tumors. Mol Ther 2014;22:1266–74.
[113] Dai MS, Nitcheu-Tefit J, Alcock S. Development of an Escherichia coli expressing listeriolysin-O vac-
cine against Wilms tumor gene 1-expressing tumors. J Immunother 2009;32(8):845–55.
[114] Gunn GR, Zubair A, Peters C, et al. Two Listeria monocytogenes vaccine vectors that express different
molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell
immunity that correlates with their ability to induce regression of established tumors immortalized
by HPV-16. J Immunol 2001;167(11):6471–9.
[115] Singh R, Dominiecki ME, Jaffee EM, Paterson Y. Fusion to Listeriolysin O and delivery by Listeria
monocytogenes enhances the immunogenicity of HER-2/neu and reveals subdominant epitopes in the
FVB/N mouse. J Immunol 2005;175(6):3663–73.
[116] Toussaint B, Chauchet X, Wang Y, et al. Live-attenuated bacteria as a cancer vaccine vector. Expert
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Rev Vaccines 2013;12:1139–54.
[117] Wallecha A, Carroll KD, Maciag PC, et al. Multiple effector mechanisms induced by recombinant
Listeria monocytogenes anti-cancer immunotherapeutics. Adv Appl Microbiol 2009;66:1–27.
[118] Chou CK, Hung JY, Liu JC, et al. An attenuated Salmonella oral DNA vaccine prevents the growth of
hepatocellular carcinoma and colon cancer that express alpha-fetoprotein. Cancer Gene Ther
2006;13:746–52.
[119] Xiang R, Lode HN, Chao TH, et al. An autologous oral DNA vaccine protects against murine mel-
anoma. Proc Natl Acad Sci U S A 2000;97:5492–7.
[120] Xiang R, Primus FJ, Ruehlmann JM, et al. A dual-function DNA vaccine encoding
carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity
against colon cancer in carcinoembryonic antigen-transgenic mice. J Immunol 2001;167(8):4560–5.
[121] Niethammer AG, Xiang R, Becker JC, et al. A DNA vaccine against VEGF receptor 2 prevents effec-
tive angiogenesis and inhibits tumor growth. Nat Med 2002;8(12):1369–75.
[122] Schmitz-Winnenthal FH, Hohmann N, Schmidt T, et al. A phase 1 trial extension to assess immu-
nologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against
VEGFR2, in patients with advanced pancreatic cancer. Onco Targets Ther 2018;7(4), e1303584.
[123] Bowen WS, Svrivastava AK, Batra L. Current challenges for cancer vaccine adjuvant development.
Expert Rev Vaccines 2018;17(3):207–15.
[124] Agorio C, Schreiber F, Sheppard M, et al. Live attenuated Salmonella as a vector for oral cytokine gene
therapy in melanoma. J Gene Med 2007;9(5):416–23.
[125] Sorenson BS, Banton KL, Frykman NK, et al. Attenuated Salmonella typhimurium with IL-2 gene
reduces pulmonary metastases in murine osteosarcoma. Clin Orthop Relat Res 2008;466(6):1285.
[126] Saltzman DA, Heise CP, Hasz DE, et al. Attenuated Salmonella typhimurium containing interleukin-2
decreases MC-38 hepatic metastases: a novel anti-tumor agent. Cancer Biother Radiopharm 1996;11
(2):145–53.
[127] Saltzman DA, Katsanis E, Heise CP, et al. Antitumor mechanisms of attenuated Salmonella typhimurium
containing the gene for human interleukin-2: a novel antitumor agent? J Pediatr Surg 1997;32
(2):301–6.
[128] Loeffler M, Le’Negrate G, Krajewska M, Reed JC. IL-18-producing Salmonella inhibit tumor growth.
Cancer Gene Ther 2008;15:787–94.
[129] Loeffler M, Le’Negrate G, Krajewska M, Reed JC. Attenuated Salmonella engineered to produce
human cytokine LIGHT inhibit tumor growth. Proc Natl Acad Sci U S A 2007;104:12879–83.
[130] Loeffler M, Le’Negrate G, Krajewska M, Reed JC. Salmonella typhimurium engineered to produce
CCL21 inhibit tumor growth. Cancer Immunol Immunother 2009;58:769–75.
[131] Yoon WS, Choi WC, Sin JI, Park YK. Antitumor therapeutic effects of Salmonella typhimurium con-
taining Flt3 ligand expression plasmids in melanoma-bearing mouse. Biotechnol Lett 2007;29:511–6.
[132] Yoon W, Park YC, Kim J, et al. Application of genetically engineered Salmonella typhimurium for
interferon-gamma-induced therapy against melanoma. Eur J Cancer 2017;70:48
[133] Yuhua L, Kunyuan G, Hui C, et al. Oral cytokine gene therapy against murine tumor using attenuated
Salmonella typhimurium. Int J Cancer 2001;94(3):438–43.
[134] Arellano M, Lonial S. Clinical uses of GM-CSF, a critical appraisal and update. Biol Theory 2008;2
(1):13–27.
[135] Strauss J, Heery CR, Kim JW, et al. First-in-human phase I trial of a tumor-targeted cytokine (NHS-
IL12) in subjects with metastatic solid tumors. Clin Cancer Res 2019;25(1):99–109.
[136] Denoncin K, Collet JF. Disulfide bond formation in the bacterial periplasm: major achievements and
challenges ahead. Antioxid Redox Signal 2013;19(1):63–71.
[137] Schneewind O, Missiakas DM. Protein secretion and surface display in Gram-positive bacteria. Philos
Trans R Soc Lon Ser B Biol Sci 2012;367(1592):1123–39.
[138] Green ER, Mecsas J. Bacterial secretion systems: an overview. Microbiol Spectr 2016;4(1):10.
[139] Yoon SH, Kim SK, Kim JF. Secretory production of recombinant proteins in Escherichia coli. Recent
Pat Biotechnol 2010;4:23–9.
[140] Freudl R. Signal peptides for recombinant protein secretion in bacterial expression systems. Microb
Cell Fact 2018;17(1):52.
–61.
61Engineered microbes for cancer immunotherapy
62 Aoife M. Brennan et al.
[141] Chowdhury S, Castro S, Coker C, et al. Programmable bacteria induce durable tumor regression and
systemic antitumor immunity. Nat Med 2019;25(7):1057–63.
[142] Gurbatri CR, Lia I, Vincent R, et al. Engineered probiotics for local tumor delivery of checkpoint
blockade nanobodies. Sci Transl Med 2020;12(530), eaax0876.
[143] Zheng JH, Nguyen VH, Jiang SN, et al. Two-step enhanced cancer immunotherapy with engineered
Salmonella typhimurium secreting heterologous flagellin. Sci Transl Med 2017;9(376), eaak9537.
[144] Schmitz-Winnenthal FH, Hohmann N, Niethammer AG, et al. Anti-angiogenic activity of VXM01,
an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: a ran-
domized, placebo-controlled, phase 1 trial. Onco Targets Ther 2015;4(4), e1001217.
[145] Marabelle A, Andtbacka R, Harrington K, et al. Starting the fight in the tumor: expert recommen-
dations for the development of human intratumoral immunotherapy (HIT-IT). Ann Oncol 2018;29
(11):P2163–74.
[146] Park SH, Zheng JH, Nguyen VH, et al. RGD peptide cell-surface display enhances the targeting and
therapeutic efficacy of attenuated Salmonella-mediated cancer therapy. Theranostics 2016;6
(10):1672–82.
[147] Pinero-Lambea C, Bodelon G, Fernandez-Perianez R, et al. Programming controlled adhesion of
E. coli to target surfaces, cells, and tumors with synthetic adhesins. ACS Synth Biol 2015;4(4):463–73.
[148] Van Dessel N, Swofford CA, Forbes NS. Potent and tumor specific: arming bacteria with therapeutic
proteins. Ther Deliv 2015;6(3):385–99.
[149] European Pharmacopoeia Commission 3053E. General monograph on live biotherapeutic products.
Eur Pharm Suppl 2019;9(7).
CHAPTER THREE
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Polymeric scaffolds for antitumor
immune cell priming
Khushbu Bhatta, Loek J. Eggermontb, and Sidi A. Bencherif
a
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, United States
b
Department of Chemical Engineering, Northeastern University, Boston, MA, United States
c
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States
d
Department of Bioengineering, Northeastern University, Boston, MA, United States
e
Sorbonne University, UTC CNRS UMR 7338, Biomechanics and Bioengineering (BMBI), University of Technology of
Compie`gne, Compie`gne, France
b,c,d,e
Contents
1. Introduction 63
2. Polymeric materials and scaffold systems 66
3. Polymeric scaffolds for DC priming and activation 75
4. Polymeric scaffolds for T-cell activation 81
5. Conclusion and future perspectives 86
References 87
1. Introduction
Cancer is a life-threatening disorder, and is the second-leading cause of death
worldwide, with an estimated 606,520 deaths projected in the USA alone for 2020
[1]. Traditional treatments such as radiation, chemotherapy, and targeted cancer therapies
have been associated with limited efficacy, leading to drug resistance, toxicity, and minimal survival benefit [2–4]. Immunotherapy has emerged as a breakthrough therapeutic
option for cancer. The advent of immune checkpoint inhibitors (ICIs), cancer vaccines,
and chimeric antigen receptor (CAR) T cell-based adoptive therapies have revolutionized treatment paradigms. Even though the concept of immunotherapy has existed for
centuries, the approach of harnessing the body’s immune system to eradicate tumors
gained momentum after the impressive clinical results of ICIs [5,6].
Dendritic cells (DCs) are antigen-presenting cells (APCs) that play a central role in
orchestrating antitumor immune responses [7]. During tumor development, they cap-
ture, process, and present tumor antigens on major histocompatibility complex
(MHC) proteins [8]. Thereafter, activated DCs travel to draining lymph nodes to prime
antigen-specific naı¨ve T cells by presenting the antigen-MHC complex along with
Engineering Technologies and Clinical Translation Copyright © 2022 Elsevier Inc.
All rights reserved.https://doi.org/10.1016/B978-0-323-90949-5.00003-6
63
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