Publications – Laboratory for Synthetic Immunity

Journal Publications

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† equal contribution | ‡ co-corresponding author

2024
1. Su FY†, Siebart JC†, Chan CS†, Wang MY, Yao X, Silva Trenkle AD, Sivakumar A, Su M, Harandi R, Shahrawat N, Nguyen CH, Goenka A, Mun J, Dhodapkar MV, and Kwong GA, “Antigen-specific T cell immunotherapy by in vivo mRNA delivery” bioRxiv 2024. [DOI: 10.1101/2024.10.29.620946]
2. Gamboa L†, Zamat AH†, Thiveaud CA, Lee HJ, Kulaksizoglu E, Zha Z, Campbell NS, Chan CS, Fábrega S, Oliver SA, Su FY, Phuengkham H, Vanover D, Peck HE, Sivakumar A, Dahotre SN, Harris AM, Santangelo PJ, and Kwong GA, “Sensitizing solid tumors to CAR-mediated cytotoxicity by lipid nanoparticle delivery of synthetic antigens” Nat. Cancer, in press (2024).
3. Sivakumar A, Phuengkham H, Rajesh H, Mac QD, Silva Trenkle AD, Rogers LC, Bawage SS, Hincapie R, Li Z, Vainikos S, Lee I, Xue M, Qiu P, Finn M.G., and Kwong GA, “Activity-based nanosensors that implement AND-gate logic for programmable detection of antitumor immunity” Nat. Nanotechnol., in press (2024).
4. Gorti V, McCubbins K, Houston D, Silva Trenkle AD, Holberton A, Serafini CE, Wood L, Kwong GA, and Robles FE, “Quantifying UV-induced photo-damage for longitudinal live-cell imaging applications of deep-UV microscopy” Biomed. Opt. Express 16, 208–221 (2025). [DOI: 10.1364/BOE.544778]
5. Wu Y, Huang Z, Liu Y, He P, Wang Y, Yan L, Wang X, Gao S, Zhou X, Yoon CW, Sun K, Situ Y, Phuong H, Yuan Z, Zhu L, Zhou Q, Zhao Y, Liu T, Kwong GA, Chien S, Liu L, and Wang Y. “Ultrasound control of genomic regulatory toolboxes for cancer immunotherapy” Nat. Commun. 15, 10444 (2024). [DOI: 10.1038/s41467-024-54477-7]
6. Siebart JC†, Chan CS†, Yao X, Su FY, and Kwong GA, “In vivo gene delivery to immune cells” Curr. Opin. Biotechnol. 88, 103169 (2024). [DOI: 10.1016/j.copbio.2024.103169]
7. Hua X, Han K, Mandracchia B, Radmand A, Liu W, Kim H, Yuan Z, Ehrlich SM, Li K, Zheng C, Son J, Silva Trenkle AD, Kwong GA, Zhu C, Dahlman JE, and Jia S, “Light-field flow cytometry for high-resolution, volumetric, and multiparametric 3D single-cell analysis” Nat. Commun. 15, 1975 (2024). [DOI: 10.1038/s41467-024-46250-7]
8. Kinney BLC, Gunti S, Kansal V, Parrish CJ, Saba NF, Teng Y, Henry MK, Su FY, Kwong GA, and Schmitt NC, “Rescue of NLRC5 expression restores antigen processing machinery in head and neck cancer cells lacking functional STAT1 and p53” Cancer Immunol Immunother 73, 10 (2024). [DOI: 10.1007/s00262-023-03589-y]

2023
1. Son J, Mandracchia B, Silva Trenkle AD, Kwong GA, and Jia S. “Portable light-sheet optofluidic microscopy for 3D fluorescence imaging flow cytometry” Lab-on-a-chip 23, 624–630 (2023). [DOI: 10.1039/D2LC01024K]

2022

Holt BA†, Lim HS†, Sivakumar A, Phuengkham H, Su M, Tuttle M, Liakakos H, Qiu P‡, and Kwong GA‡, “Embracing enzyme promiscuity with activity-based compressed biosensing” Cell Reports Methods 3, 100372 (2022). [DOI: 10.1016/j.crmeth.2022.100372]
Su FY, Zhao QY, Dahotre SD, Gamboa L, Bawage SS, Silva Trenkle AD, Zamat A, Phuengkham H, Ahmed R, Santangelo P, and Kwong GA, “In vivo mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles” Sci. Adv. 8: eabm7950 (2022). [DOI: 10.1126/sciadv.abm7950]
Mac QD†, Sivakumar A†, Phuengkham H, Xu C, Bowen JR, Su FY, Stentz SZ, Sim H, Harris AM, Li TT, Qiu P, and Kwong GA, “Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors” Nat. Biomed. Eng. 6, 320–324 (2022). [DOI: doi.org/10.1038/s41551-022-00852-y]

Summary \| Since 2014, the FDA has approved 7 immune checkpoint inhibitors, but not all patients benefit from therapy. We developed a new class of immune checkpoint inhibitor that is attached with protease sensors for early detection of drug treatment. In preclinical studies, we found that these therapeutic sensors can indicate early responses before future changes in tumor volume, and can identify different types of resistance as they emerge.

Press Coverage \| Georgia Tech Research “Kwong lab develops biosensors for quick assessment of cancer treatment” \| Inside Precision Oncology “Biosensors created to detect early response to immune checkpoint blockade” \| MedicalXpress \| Technology.org \| EurekAlert! \| ScienMag \| Newswise \| Bioengineer.org \| The Medical News \| Technology Networks \| ecancer

Holt BA, Tuttle M, Xu Y, Su M, Roise JJ, Wang X, Murthy N and Kwong GA, “Dimensionless parameter predicts bacterial prodrug success” Mol. Syst. Biol. 18: e10496 (2022). [DOI: 10.15252/msb.202110495]

2021

Cazanave SC, Warren AD, Pacula M, Touti F, Zagorska A, Gural N, Huang EK, Sherman S, Cheema M, Ibarra S, Serer A, Bates J, Billin AN, Liles JT, Budas GR, Breckenridge DG, Tiniakos D, Ratziu V, Daly AK, Govaere O, Anstee QM, Gelrud L, Luther J, Chung RT, Corey KE, Winckler W, Bhatia SN, and Kwong GA, “Peptide-based urinary monitoring of fibrotic non-alcoholic steatohepatitis by mass barcoded activity-based sensors” Sci. Transl. Med. 13, eabe8939 (2021). [DOI: 10.1126/scitranslmed.abe8939]

Summary \| Nonalcoholic steatohepatitis (NASH) is a type of fatty liver disease that has been dubbed the silent epidemic as it has few symptoms. When left undiagnosed and untreated, the liver can develop cirrhosis or liver cancer. We developed synthetic biomarkers to diagnosis NASH early, monitor changes in disease severity, and indicate response to treatment.

Miller IC†, Zamat A†, Sun LK, Phuengkham H, Harris AM, Gamboa L, Yang J, Murad JP, Priceman SJ and Kwong GA, “Enhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control” Nat. Biomed. Eng. 5, 1348–1359 (2021). [DOI: 10.1038/s41551-021-00781-2]

Summary \| Treating solid tumors with chimeric antigen receptor (CAR) T cells typically results in poor responses. In this study, we developed a new class of CAR T cells that are switched on by localized heating to release potent biologics that are otherwise too toxic to use systemically. Thermal targeting of CAR T cells opens the door for spatial control to potentiate cancer therapy.

Press Coverage \| Georgia Tech Research Horizons “Heat-controllable CAR T-cells destroy tumors and prevent relapse in new study” \| TheScientist “Heating up CAR T cells for cancer therapy” \| GEN “CAR T gets hot under the collar for cancer targets” \| Inside Precision Medicine “CAR T cell modifications show improvement for treating solid tumors” \| Newswise \| MedicalXpress \| The Medical News \| Technology Networks \| AZO Life Sciences \| Front Line Genomics \| Science Daily \| The Science Advisory Board

Kwong GA‡, Ghosh S, Gamboa L, Patriotis C, Srivastava S‡, and Bhatia SN‡, “Synthetic Biomarkers: A 21st century path to early cancer detection” Nat. Rev. Cancer 21, 655–668 (2021). [DOI: 10.1038/s41568-021-00389-3]

Summary | In 2019, the NCI Division of Cancer Prevention co-organized a think tank meeting on synthetic biomarkers for early detection. We wrote this review to summarize the current science and as a clarion call for more scientists and engineers to work together to solve this important problem. We also dedicated the article to the late Dr. Sam Gambhir, a visionary pioneer and thought leader in bioengineering who devoted his career to developing methods for early disease detection.

Bazrafshan A, Kyriazi ME, Holt BA, Deng W, Piranej S, Su H, Hu Y, El-Sagheer A, Brown T, Kwong GA, Kanaras A, and Salaita K, “DNA gold nanoparticle motors demonstrate processive motion with bursts of speed up to 50 nm per second” ACS Nano 15(5), 8427–8438 (2021). [DOI: 10.1021/acsnano.0c10658]
Su FY†, Mac QD†, Sivakumar A, and Kwong GA, “Interfacing biomaterials with synthetic T cell immunity” Adv. Healthcare Mater. 10, 2100157 (2021). [DOI: 10.1002/adhm.202100157]
Dahotre SN†, Romanov A†, Su FY, and Kwong GA, “Synthetic antigen-presenting cells for adoptive T cell therapy” Adv. Therap. 4, 2100034 (2021). [DOI: 10.1002/adtp.202100034]

2020

Turner TC†, Sok MCP†, Hymel LA†, Pittman F, York WY, Mac QD, Vishna S, Lim HS, Kwong GA, Qiu P, and Botchwey EA, “Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy” Sci. Adv. 6(44), eaba7702 (2020). [DOI: 10.1126/sciadv.aba7702]
Holt BA and Kwong GA, “Protease circuits for processing biological information” Nat. Commun. 11, 5021 (2020). [DOI: 10.1038/s41467-020-18840-8]

Summary \| Biological circuits engineered to interface with living systems will enable new applications for programmable immune therapies and diagnostics. In this study, we explored how treating proteases as ‘biological bits’ could be used to design cell-free biocircuits with the capacity to perform digital operations such as analog-to-digital conversion for drug delivery, as well as analog operations that implement ‘fuzzy logic’ to solve mathematical problems.

Press Coverage \| Georgia Tech Research Horizons “‘Programmable Medicine’ is the goal for new bio-circuitry research” \| Phys.org \| Mirage News \| TMR Blog

Gamboa L^†, Zamat A^† and Kwong GA, “Synthetic immunity by remote control” Theranostics 10(8): 3652–3667 (2020). [DOI: 10.7150/thno.41305]
Kwong GA, “Macrophage sensors for early cancer detection” Clin. Chem. 66(2), 268–270 (2020). [DOI: 10.1093/clinchem/hvz017]
Tadros AR, Romanyuk A, Miller IC, Santiago A, Noel RK, O’Farrell L, Kwong GA and Prausnitz MR, “STAR particles for enhanced topical drug and vaccine delivery” Nat. Med. 26, 341–347 (2020). [DOI:10.1038/s41591-020-0787-6]
Gamboa L, Phung EV, Li H, Meyers JP, Miller IC and Kwong GA, “Heat-triggered remote control of CRISPR-dCas9 for tunable transcriptional modulation” ACS Chem. Biol. 15(2), 533–542 (2020). [DOI: 10.1021/acschembio.9b01005]

Summary | CRISPR-based approaches have achieved wide success in modulating gene activity to control cell function and are potential tools for clinical therapies. However, the lack of precise methods to deliver and control Cas protein expression in vivo remains a critical hurdle. Here we develop a tunable, heat-triggered platform that regulates mammalian cell transcription by remote control of dCas9 transcriptional modulators.

2019

Zhuang Q^†, Holt BA^†, Kwong GA^‡ and Qiu P^‡, “Deconvolving multiplexed protease signatures with substrate reduction and activity clustering” PLoS Comput. Biol. 15(9): e1006909 (2019). [DOI: 10.1371/journal.pcbi.1006909]
Mac QD^†, Mathews DV^†, Kahla JA, Stoffers C, Delmas OM, Holt BA, Adams AB^‡ and Kwong GA^‡, “Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity” Nat. Biomed. Eng. 3, 281–291 (2019). [DOI: 10.1038/s41551-019-0358-7]

Summary \| The current diagnostic “gold” standard to monitor transplant patients for signs of organ rejection is the tissue biopsy. However, this procedure is invasive and lacks the ability to detect rejection at an early stage. We developed immune sensors that sense anti-graft immune activity from recipient urine, allowing noninvasive detection at the onset of transplant rejection.

Press Coverage \| Georgia Tech Research Horizons “Urine test detects organ transplant rejection, could replace needle biopsies” \| Nature Rev Nephrology “Nanosensors enable early detection of acute T cell-mediated rejection of transplants” \| Nature BME “Urinary nanosensors of early transplant rejection” \| EurekAlert! “Fluorescing urine signals organ transplant rejection, could replace needle biopsies” \| Medical Design and Outsourcing “How urine tests could detect organ transplant rejection and eliminate needle biopsies” \| Newswise \| TECHExplorist \| LongRoom \| The Medical News \| Science Daily \| Medical Xpress \| GENbio \| MD linx \| MDedge \| Medical Health News \| Pediatric News \| Medgadget \| ECNmag \| InsiderAdvantage \| Wearable Technologies \|

Dahotre SN, Chang YM, Romanov AM and Kwong GA, “DNA-barcoded pMHC tetramers for detection of single antigen-specific T cells by digital PCR” Anal. Chem. 91(4), 2695–2700 (2019). [DOI: 10.1021/acs.analchem.8b04153]

2018

Holt BA, Mac QD and Kwong GA, “Nanosensors to detect protease activity in vivo for noninvasive diagnostics” J. Vis. Exp. (130), e37937, (2018). [DOI: 10.3791/57937]

<a title="Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics" href="https://www.jove.com/video/57937/nanosensors-to-detect-protease-activity-vivo-for-noninvasive">Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics</a> <p></p>

Miller IC, Gamboa Castro M, Maenza J, Weis JP and Kwong GA, “Remote control of mammalian cells with heat-triggered gene switches and photothermal pulse trains” ACS Synth. Biol. 7(4), 1167–1173 (2018). [DOI: 10.1021/acssynbio.7b00455]

Summary | Genetically engineered T cells have the potential to cure patients of cancer. Yet after they are infused into recipients, we lack the ability to control their activity throughout the body including at disease sites. Here we genetically engineer T cells to allow them to be remotely controlled using pulses of heat localized by laser light. This could improve the precision of T cell therapies for cancer.

Dahotre SN, Chang YM, Wieland A, Stammen SR and Kwong GA, “Individually addressable and dynamic DNA gates for multiplexed cell sorting” Proc. Natl. Acad. Sci. USA 115(17), 4357–4362 (2018). [DOI: 10.1073/pnas.1714820115]

2016
1. Dudani JS, Buss CG, Akana RTK, Kwong GA and Bhatia SN, “Sustained-release synthetic biomarkers for monitoring thrombosis and inflammation using point-of-care compatible readouts” Adv. Funct. Mater. 26(17), 2919–2928 (2016). [DOI: 10.1002/adfm.201505142]

2015
1. Dudani JS, Jain PK, Kwong GA, Stevens KR and Bhatia SN, “Photoactivated spatiotemporally-responsive nanosensors of in vivo protease activity” ACS Nano 9(12), 11708–11717 (2015). [DOI: 10.1021/acsnano.5b05946]
2. Kwong GA, Dudani JS, Carrodeguas E, Mazumdar EV, Zekavat MS and Bhatia SN, “Mathematical framework for activity-based cancer biomarkers” Proc. Natl. Acad. Sci. USA 112(41), 12627–12632 (2015). [DOI: 10.1073/pnas.1506925112]
3. Danino T^†, Prindle A^†, Kwong GA, Skalak M, Li H, Allen K, Hasty J and Bhatia SN, “Programmable probiotics for detection of cancer in urine” Sci. Transl. Med. 7(289), 289ra84 (2015). [DOI: 10.1126/scitranslmed.aaa3519]

2014 & Earlier

Warren AD, Gaylord ST, Ngan KC, Milutinovic MD, Kwong GA, Bhatia SN and Walt DR, “Disease Detection by Ultrasensitive Quantification of Microdosed Synthetic Urinary Biomarkers” J. Am. Chem. Soc. 136(39), 13709–13714 (2014). [DOI: 10.1021/ja505676h]
Lin KY, Lo JH, Consul N, Kwong GA and Bhatia SN, “Self-titrating anticoagulant nanocomplexes that restore homeostatic regulation of the coagulation cascade” ACS Nano 8(9), 8776–8785 (2014). [DOI: 10.1021/nn501129q]
Warren AD^†, Kwong GA^†, Wood DK^†, Lin KY and Bhatia SN, “Point-of-care diagnostics for noncommunicable diseases using synthetic urinary biomarkers and paper microfluidics” Proc. Natl. Acad. Sci. USA 1119(10), 3671–3676 (2014). [DOI: 10.1073/pnas.131465111]

Summary | Meeting global health challenges will require cheap diagnostics to be deployed in resource-limited environments. We developed low-cost paper tests for detecting diseases from urine, similar to commercial home pregnancy tests. Our test strips do not require expensive instruments, and could lead to better identification of patients with diseases in settings where access to healthcare is limited.

Press Coverage | MIT News “A paper diagnostic for cancer” | FOX News “Simple paper urine test may detect cancer, blood clots” | 90.9 wbur (Boston’s NPR) “Research explores pregnancy-type test for detecting cancer” | CNET “Pee here to find out if you have cancer” | Science News “Urine test detects not pregnancy but cancer” | Wired “Get an injection, pee on a stick, get a cancer diagnosis” | Gizmodo “New paper-based urine tests could detect cancer and heart disease” | Medical News Today “Cheap urine test for cancer steps closer” | Smart Planet “Paper test strip detects cancer in minutes” | New Scientist “Cancer diagnosis as simple as a pregnancy test”

Lin KY^†, Kwong GA^†, Warren AD, Wood DK and Bhatia SN, “Nanoparticles that sense thrombin activity as synthetic biomarkers of thrombosis” ACS Nano 7(10), 9001–9009 (2013). [DOI: 10.1021/nn403550c]

Summary | Blood clots are dangerous as they can break off and lodge in small blood vessels, which can cause pulmonary embolism in the lungs or a stroke in the brain. We developed miniaturized biosensors to sense the activity of thrombin – the key enzyme involved in clot formation – that could help detect blood clots before they become an issue.

Press Coverage | MIT News “Finding blood clots before they wreak havoc” | The Economist “Particle Physiology” | Huffington Post “Test to detect hidden blood clots on the horizon” | ACS “Toward a urine test for detecting blood clots” | AzoNano “Blood clots chop peptides added onto nanomaterials” | Medical News Today “Nanotechnology urine test could detect deadly blood clots” | Health Central “Urine test could find blood clots early” | HealthLine “Simple urine test spots dangerous blood clots”

Kwong GA, von Maltzahn G, Murugappan G, Abudayyeh O, Mo S, Papayannopoulos IA, Sverdlov D, Liu SB, Warren AD, Popov Y, Schuppan D and Bhatia SN, “Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease” Nat. Biotechnol. 31, 63–70 (2013). [DOI: 10.1038/nbt.2464]

Summary | Catching cancer at an early stage markedly improves patient prognosis, yet current blood biomarkers lack the sensitivity to indicate small tumors when they are most responsive to treatments. We pioneered the first class of nano-scale biological sensors for early cancer detection. These engineered biomarkers circulate in the body, survey for nascent tumor sites, and report on their activity by shedding detection signals into urine. This noninvasive technology could lead to earlier diagnosis and following response to treatment.

Press Coverage | MIT news “New technology may enable early cancer diagnosis” | Phys.org “Nanoparticles amplify tumor signals, making them easier to detect in the urine” | Cancer Discovery “Synthetic biomarkers identify early cancer” | FierceHealthIT “Nanotechnology enables creation of biomarkers for early cancer detection” | AZoNano “Novel nanoparticles for easier biomarker detection” | NZZ am Sonntag | Nanomedicine | Newsroom America | ProteoMonitor | National Cancer Institute

Millward SW, Henning R, Kwong GA, Pitram S, Agnew HD, Deyle KM, Nag A, Hein J, Lee SS, Lim J, Pfeilsticker JA, Sharpless KB and Heath JR, “Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for Akt1” J. Am. Chem. Soc. 133, 18280–88 (2011). [DOI: 10.1021/ja2064389]
Vermesh U^†, Vermesh O^†, Wang J, Kwong GA, Ma C, Hwang K and Heath JR, “High-density, multiplexed patterning of cells at single-cell resolution for tissue engineering and other applications” Angew. Chem. 50, 7378–80 (2011). [DOI: 10.1002/anie.201102249]
Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya R, Liu C, Kwong GA, Radu C, Ribas A and Heath JR, “A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells” Nat. Med. 17, 738–43 (2011). [DOI: 10.1038/nm.2375]
Kwong GA, Radu CG, Shu J, Koya R, Comin-Anduix B, Hadrup S, Bailey RC, Witte ON, Schumacher TN, Ribas A and Heath JR, “Modular nucleic acid assembled p/MHC microarrays for multiplexed sorting of antigen-specific lymphocytes” J. Am. Chem. Soc. 131(28), 9695-703 (2009). [DOI: 10.1021/ja9006707]
Fan R, Vermesh O, Srivastava A, Yen B, Qin L, Ahmad H, Kwong GA, Liu C, Gould J, Hood L and Heath JR, “Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood” Nat. Biotechnol. 26(12), 1373–8 (2008). [DOI: 10.1038/nbt.1507]
Bailey RC, Kwong GA, Radu CG, Witte ON and Heath JR, “DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins” J. Am. Chem. Soc. 129(7), 1959–67 (2007). [DOI: 10.1021/ja065930i]
Bunimovich Y, Shin Y, Yeo W, Amori M, Kwong GA and Heath JR, “Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solutions” J. Am. Chem. Soc. 128(50), 16323–31 (2006). [DOI: 10.1021/ja065923u]