- Siebart JC†, Chan CS†, Yao X, Su FY, and Kwong GA, “In vivo gene delivery to immune cells” submitted (2023).
- Gamboa L, Zamat AH, Vanover D, Thiveaud CA, Peck HE, Phuengkham H, Sivakumar A, Harris AM, Dahotre SN, Su FY, Santangelo PJ, and Kwong GA, “Sensitizing solid tumors to CAR-mediated cytotoxicity using synthetic antigens” bioRxiv 2021.12.11.472238 preprint.
- Wu Y, Huang Z, Liu Y, Yoon CW, Situ Y, Ho P, Yuan Z, Zhu L, Zhao Y, Liu T, Kwong GA, Chien S, Wang Y, “Spatiotemporal control of genomics and epigenomics by ultrasound” submitted (2023).
- 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]
- 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]
- 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]
- 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.
- 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]
- 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]
- 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. Press Coverage | Georgia Tech Research Horizons “Remote-control shoots laser at nano-gold to turn on cancer-killing immune cells” | ASME “Precisely targeting tumors with cancer fighting T cells” | Medical News Today “This ‘genetic switch’ could help fight cancer” | Science Daily | Controlled Environments | Phys.org | EurekAlert! | Nanowerk | Nanotechnology Now | Medgadget “Remote-controlled signal activates T cells for cancer immunotherapy”
- 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]