//Background//---
It passes over 1.5 years after SARS-CoV-2 pandemic. The total number
of the patients is about 185 million, but the degree of symptom is highly
variant for each patient from asymptomatic to severe symptom. Ideally, there is
the most suitable therapy per a patient. However, we need to adopt the common
therapy set due to the logistic and the cost matter. In the precise medicine,
our purpose is to find the suitable therapeutic method as much as possible. To
realize this, both precise diagnostic and targeting at the lesion are
prerequisite.
Monica P. McNerney, Kailyn E. Doiron, Tai L. Ng, Timothy Z. Chang
& Pamela A. Silver review about “Theranostic cell” in a pleiotropic fashion, both therapy and diagnosis by
bacterial/mammalian cell(1). We hope to share a small part of these contents
with the global important readers. Firstly, I tick off current status,
challenging matter, opportunities as background in this letter.
---
(Current status)
*Invasive biopsies and subsequent
pathological analysis is necessary(2-4).
---
(Challenging matter)
*Systemic action for many therapies,
whereby the risk of off-target effects even in the targeted therapy(5).
---
(Opportunities)
*Early advances in synthetic biology
(multidisciplinary biological research including bioengineering) enable us to
create arbitrary cells that have specific receptors to active native
pathway(6).
*”Theranostic” cells, which can serve as both (*1)diagnostic tools and (*2)drug
delivery system, such as the cell-specific delivery system, (*3)therapeutics(1).
(*1)Diagnostic tools: Ex vivo blood
testing, Real-time health tracking, Analysis of microbiome from feces.
(*2)Drug delivery system: Cell expressing
the surface receptor with high affinity to the target cell and tissue
(*3)Therapeutics: Cancer targeting,
Immunomodulation, Microbiome modulation
*Approved theranostic cells: Chimeric
antigen receptor (CAR) T cell therapy for blood cancer(7-10).
*Faster subsequent engineering(11),
high-throughput screening(12), robust/rapid characterization even in the
complex environment(13-15) could develop the therapy through theranostic cells.
//(*1)Bacterial diagnostic(1)//---
(Ex vivo)
*Ions, metabolites and peptides based
compounds are analyzed through advanced machinery and extensive sample
processing(16,17)
*Whole-cell diangnositc:
Engineering bacterial cells so as to respond analyte such as
micronutrients and sugar(18-20). Bacterial sensor, which can detect pathogenic
bacterial cell-to-cell communication (quorum-sensing system)(21).
*Cell-free diagnositcs:
Sensing
a mixture of nucleic acids, metabolites and proteins through biological-based
sensing platform can detect diverse biomarkers(22). This can be applied to
virus such as Ebola(23), Zika(24) and SARS-CoV-2(25).
---
(In vivo)
*Sensing internally biomarker in a
minimally invasive manner.
*Microbiome diagnostics:
Gut
microbiome have potentially stable/long-term reporters on the current physical
state. However, the environmental factor is highly complex, we need to find the
reliable biomarker which can be analyzed by blood sample and stool sample.
*Real-time reporting:
Devises, which can transmit signals from
inside the body, resulting real-time health reports. Engineering bacteria
responding to specific light wavelength and radio wave(See Fig.2Bb). However,
this method hasn’t been tested in humans yet.
//Mammalian cell diagnostics(1)//---
*Current technological development enables
us to control complex eukaryotic cell output at the Transcriptional /
Translational / Post-translational level, meaning control of gene
regulation(26-28).
---
(Ex vivo)
*Immune reactions in the skin for specific
allergens
*Immune reactions by engineering HEK293
cell through histamine(Immune effector)(29)
---
(In vivo)
*Less common
*Sensor for hypercalcaemia(Calcium
detection)(41), but having immunogenic matter.
// Mammalian cell therapeutics(1)//---
(Synthetic TCR T cell)
*T cell receptor(TCR)-modified T cells for
improving effector function to cancer.
*MHC proteins is engineered to
target-specific peptides(30).
*Clinical state:
Successful for myeloma/melanoma(31,32),
others are underway(33).
---
(CAR-T cells)
*CAR T cells were engineered to sense
cancer biomarkers, evolve cytotoxic response for cancer tissue. Tumor-specific
antigen specific recognition(See Fig.4A)
*We can harness intracellular domain in T
cell for cytotoxic response((1)See Fig.4A), leading to persistence(34).
*Challenging matter:
1: On-target off-tumor killing of healthy
cells(35).
2: Antigen escape leads to low binding
affinity(36).
3: Side effect such as neurotoxicity and
cytokine release syndrome(37)
*Improvement
1: Inducible CAR-T suicide function(See
Fig.4Ba)
2: Inhibitory receptor (specific recognition
of healthy cell)(See Fig.4Bb)
3: Receptor expression-level modulation(See
Fig.4Bc)
4: And gate recognition(Simultaneous two
receptor recognition) (See Fig.4Bd)
5: Avidity tuning by the receptors more
than one(See Fig.4Be)
6: Antigen switching for combating antigen
escape of cancer cell(See Fig.4Bf)
*Clinical state: Approved as autologous
cell therapy
---
(Engineered stem cells for regenerative
medicine)
*Vascular system:
Expressing vascular endothelial growth factor
(VEGF) promotes angiogenesis, which is critical to tissue regeneration(38).
//Therapeutic cost problems//---
In
mammalian cell engineering such as CAR-T cell, cost matter remains. A single
dose of tisagenlecleucel(Drug) costs about by US$40,000, total costs are
estimated by $475,000 per person. To reduce cost, we need to allogenic T cells,
which potentially eliminates the need to engineering custom therapies for each
patient(39,40), but the risk of graft-versus-host disease is open matter(34).
Therefore, immune insensitive HLA type may need to be found. On the other hand,
CAR-NK cell therapy is promising, in the past clinical study, graft-versus-host
disease is not reported(42). And adeno-virus, which is used by SARS-CoV-2
vaccine, can be harnessed as a carrier, whereby cost may be drastically
reduced.
//The cell-specific delivery system//---
As
indicated in this report by Monica P. McNerney, Kailyn E. Doiron, Tai L. Ng,
Timothy Z. Chang & Pamela A. Silver, diagnostic perspective exists also in
the cell-specific delivery system. Furthermore, we could evaluate the
efficiency of the drug delivery at the target lesion from some fingerprints in
blood and stool. Therefore, we need to consider about feasibility of the
precise medicine in a multi-phases fashion, such as targeting ability, side
effect, transformation protocol from lab-based study to clinical study,
concurrent therapeutic possibility(both surface receptor and infused drug on/in
nanoparticle), diagnosis both ex an in vivo, evaluation of the drug delivery
efficiency, cost, research collaboration and so on.
//Contributions(1)//---
M.P.M., K.E.D., T.L.N. and T.Z.C.
researched the literature and wrote the article. All authors contributed to
discussions of the content and reviewed and/or edited the manuscript.
(Reference)
(1)
Monica P. McNerney, Kailyn E. Doiron, Tai
L. Ng, Timothy Z. Chang & Pamela A. Silver
Theranostic cells: emerging clinical
applications of synthetic biology
Nature Reviews Genetics (2021)
---
Author information
Affiliations
Department of Systems Biology, Harvard
Medical School, Boston, MA, USA
Monica P. McNerney, Kailyn E. Doiron, Tai
L. Ng, Timothy Z. Chang & Pamela A. Silver
Wyss Institute for Biologically Inspired
Engineering, Harvard University, Boston, MA, USA
Monica P. McNerney, Kailyn E. Doiron, Tai
L. Ng, Timothy Z. Chang & Pamela A. Silver
(2)
Hornick, J. L.
Limited biopsies of soft tissue tumors: the
contemporary role of immunohistochemistry
and molecular diagnostics.
Mod. Pathol. 32, 27–37 (2019).
(3)
Litwin, M. S. & Tan, H.-J.
The diagnosis and treatment of prostate
cancer: a review.
JAMA 317, 2532–2542 (2017).
(4)
Smetherman, D. H.
Screening, imaging, and image-guided biopsy
techniques for breast cancer.
Surg. Clin. North. Am. 93, 309–327 (2013).
(5)
Seebacher, N. A., Stacy, A. E., Porter, G.
M. & Merlot, A. M.
Clinical development of targeted and immune
based anti-cancer therapies.
J. Exp. Clin. Cancer Res. 38, 156 (2019).
(6)
Way, J. C., Collins, J. J., Keasling, J. D.
& Silver, P. A.
Integrating biological redesign: where
synthetic biology came from and where it needs to go.
Cell 157, 151–161 (2014).
(7)
Braendstrup, P., Levine, B. L. &
Ruella, M.
The long road to the first FDA-approved
gene therapy: chimeric antigen receptor T cells targeting CD19.
Cytotherapy 22, 57–69 (2020).
(8)
FDA.
FDA approves CAR-T cell therapy to
treat adults with certain types of large
B-cell lymphoma. US Food and Drug
Administration
https://www.fda.gov/
news-events/press-announcements/fda-approves-car-t-
cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma (2017).
(9)
FDA.
FDA approves brexucabtagene autoleucel for
relapsed or refractory mantle cell lymphoma. US Food and Drug Administration
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-
mantle-cell-lymphoma (2020).
(10)
FDA.
FDA approves lisocabtagene maraleucel for
relapsed or refractory large B-cell lymphoma. US Food and Drug Administration
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-
lisocabtagene-maraleucel-relapsed-or-refractory- large-b-cell-lymphoma (2021).
(11)
Goodwin, S., McPherson, J. D. &
McCombie, W. R.
Coming of age: ten years of next-generation
sequencing technologies.
Nat. Rev. Genet. 17, 333–351 (2016).
(12)
Sarnaik, A., Liu, A., Nielsen, D. &
Varman, A. M.
High-throughput screening for efficient
microbial biotechnology.
Curr. Opin. Biotechnol. 64, 141–150 (2020).
(13)
Dijkstra, K. K. et al.
Generation of tumor-reactive T cells
by co-culture of peripheral blood lymphocytes and tumor organoids.
Cell 174, 1586–1598.e12 (2018).
(14)
Harimoto, T. et al.
Rapid screening of engineered microbial
therapies in a 3D multicellular model.
Proc. Natl Acad. Sci. USA 116, 9002–9007 (2019).
(15)
Jalili-Firoozinezhad, S. et al.
A complex human gut microbiome cultured in
an anaerobic intestine-on-a-chip.
Nat. Biomed. Eng. 3, 520–531 (2019).
(16)
Jannetto, P. J. & Fitzgerald, R. L.
Effective use of mass spectrometry in the clinical laboratory.
Clin. Chem. 62, 92–98 (2016).
(17)
Anderson, N. L.
The clinical plasma proteome: a survey of clinical assays for proteins in
plasma and serum.
Clin. Chem. 56, 177–185 (2010).
(18)
McNerney, M. P., Michel, C. L., Kishore,
K., Standeven, J. & Styczynski, M.
P.
Dynamic and tunable metabolite control for
robust minimal-equipment assessment of serum zinc.
Nat. Commun. 10, 5514 (2019).
(19)
McNerney, M. P., Piorino, F., Michel, C. L.
& Styczynski, M. P.
Active analyte import improves the dynamic range and sensitivity of a
vitamin B12 biosensor.
ACS Synth. Biol. 9, 402–411 (2020).
(20)
Courbet, A., Endy, D., Renard, E., Molina,
F. & Bonnet, J.
Detection of pathological biomarkers in
human clinical samples via amplifying genetic switches and logic gates.
Sci. Transl Med. 7, 289ra83 (2015).
(21)
Mukherjee, S. & Bassler, B. L.
Bacterial quorum sensing in complex and
dynamically changing environments.
Nat. Rev. Microbiol. 17, 371–382 (2019).
(22)
Silverman, A. D., Karim, A. S. &
Jewett, M. C.
Cell-free gene expression: an expanded
repertoire of applications.
Nat. Rev. Genet. 21, 151–170 (2020).
(23)
Pardee, K. et al.
Paper-based synthetic gene networks.
Cell 159, 940–954 (2014).
(24)
Pardee, K. et al.
Rapid, low-cost detection of zika virus
using programmable biomolecular components.
Cell 165, 1255–1266 (2016).
(25)
Joung, J. et al.
Point-of-care testing for COVID-19 using
SHERLOCK diagnostics.
Preprint at medRxiv
https://doi.org/10.1101/2020.05.04.20091231
(2020).
(26)
Lienert, F., Lohmueller, J. J., Garg, A.
& Silver, P. A.
Synthetic biology in mammalian cells: next
generation research tools and therapeutics.
Nat. Rev. Mol. Cell Biol. 15, 95–107 (2014).
(27)
Kitada, T., DiAndreth, B., Teague, B. &
Weiss, R.
Programming gene and engineered-cell
therapies with synthetic biology.
Science 359, eaad1067 (2018).
(28)
Xie, M. & Fussenegger, M.
Designing cell function: assembly of
synthetic gene circuits for cell biology applications.
Nat. Rev. Mol. Cell Biol. 19, 507–525
(2018).
(29)
Ausländer, D. et al.
A designer cell-based histamine-specific
human allergy profiler.
Nat. Commun. 5, 4408 (2014).
(30)
Clay, T. M. et al.
Efficient transfer of a tumor
antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor
reactivity.
J. Immunol. 163, 507 (1999).
(31)
Rapoport, A. P. et al.
NY-ESO-1–specific TCR-engineered
T cells mediate sustained antigen-specific antitumor effects in myeloma.
Nat. Med. 21, 914–921 (2015).
(32)
Morgan, R. A. et al.
Cancer regression in patients after transfer of genetically engineered
lymphocytes.
Science 314, 126 (2006).
(33)
Ping, Y., Liu, C. & Zhang, Y.
T-cell receptor-engineered T cells for
cancer treatment: current status and future directions.
Protein Cell 9, 254–266 (2018).
(34)
Sadelain, M., Rivière, I. & Riddell, S.
Therapeutic T cell engineering.
Nature 545, 423–431 (2017)
(35)
Majzner, R. G. & Mackall, C. L.
Clinical lessons learned from the first leg
of the CAR T cell journey.
Nat. Med. 25, 1341–1355 (2019).
(36)
Shah, N. N. & Fry, T. J.
Mechanisms of resistance to CAR T cell therapy.
Nat. Rev. Clin. Oncol. 16, 372–385 (2019).
(37)
Perales, M.-A., Kebriaei, P., Kean, L. S.
& Sadelain, M.
Building a safer and faster CAR: seatbelts,
airbags, and CRISPR. Biol.
Blood Marrow Transpl. 24, 27–31 (2018).
(38)
Nowakowski, A., Walczak, P., Janowski, M.
& Lukomska, B.
Genetic engineering of mesenchymal stem
cells for regenerative medicine.
Stem Cell Dev. 24, 2219–2242 (2015).
(39)
Qasim, W. et al.
Molecular remission of infant B-ALL after
infusion of universal TALEN gene-edited CAR
T cells.
Sci. Transl Med. 9, eaaj2013 (2017).
(40)
Benjamin, R. et al.
Genome-edited, donor-derived allogeneic
anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell
acute lymphoblastic leukaemia: results of two phase 1 studies.
Lancet 396, 1885–1894 (2020).
(41)
Tastanova, A. et al.
Synthetic biology-based cellular biomedical
tattoo for detection of hypercalcemia associated with cancer.
Sci. Transl Med. 10, eaap8562 (2018).
(42)
Enli Liu, M.D., David Marin, M.D., Pinaki
Banerjee, Ph.D., Homer A. Macapinlac, M.D., Philip Thompson, M.B., B.S., Rafet
Basar, M.D., Lucila Nassif Kerbauy, M.D., Bethany Overman, B.S.N., Peter Thall,
Ph.D., Mecit Kaplan, M.S., Vandana Nandivada, M.S., Indresh Kaur, Ph.D., Ana
Nunez Cortes, M.D., Kai Cao, M.D., May Daher, M.D., Chitra Hosing, M.D., Evan
N. Cohen, Ph.D., Partow Kebriaei, M.D., Rohtesh Mehta, M.D., Sattva Neelapu,
M.D., Yago Nieto, M.D., Ph.D., Michael Wang, M.D., William Wierda, M.D., Ph.D.,
Michael Keating, M.D., Richard Champlin, M.D., Elizabeth J. Shpall, M.D., and
Katayoun Rezvani, M.D., Ph.D.
Use of CAR-Transduced Natural Killer Cells
in CD19-Positive Lymphoid Tumors
The New England Journal of Medicine 2020;
382:545-553
---
Author Affiliations
From the Departments of Stem Cell
Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M.
Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.),
Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating),
Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.),
and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer
Center, Houston.
登録:
コメントの投稿 (Atom)
0 コメント:
コメントを投稿