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Bio

Bio


Dr. Baker is the Clinical Chief in the Division of Immunology and Rheumatology at Stanford University. He received his bachelor's degree from Pomona College, his medical degree from Harvard Medical School, and his master's degree in Epidemiology and Clinical Research from Stanford University. He completed his Internal Medicine residency at the Massachusetts General Hospital and his Rheumatology fellowship at Stanford University. Dr. Baker has established a clinical research program that is focused on clinical trials, epidemiological studies, and bench-to-bedside translational research. He has designed and led investigator-initiated studies with a focus on sarcoidosis, Sjogren?s syndrome, and IgG4-related disease. In addition, he is the Co-Director of the Stanford Multidisciplinary Sarcoidosis Program and collaborates with other team members to advance sarcoidosis clinical care and research.

Clinical Focus


  • Rheumatology
  • IgG4-related disease
  • Sjogren's syndrome
  • Sarcoidosis
  • Cardiac sarcoidosis
  • Systemic lupus erythematosus
  • ANCA-vasculitis
  • Rheumatoid Arthritis
  • Osteoarthritis

Academic Appointments


Administrative Appointments


  • Clinical Chief, Division of Immunology and Rheumatology, Department of Medicine, Stanford University (2020 - Present)

Honors & Awards


  • Translational Research and Applied Medicine Award, Stanford University (9/1/18 - 9/1/19)
  • Scientist Development Award, Rheumatology Research Foundation (2/1/17 - 1/31/18)
  • KL2 Stanford Spectrum Mentored Career Development Award, National Institutes of Health (7/1/17 - 6/30/19)
  • Distinguished Fellow Award, American College of Rheumatology (11/28/16)
  • Bevra Hahn Distinguished Fellow Scholarship, California Rheumatology Alliance (5/24/16)
  • Ruth L. Kirschstein National Research Service Award, National Institutes of Health (7/1/16 - 1/31/17)
  • ACR/EULAR Exchange Program Award, American College of Rheumatology (6/12/17)

Professional Education


  • Master of Science, Stanford University, EPIDM-MS (2019)
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2014)
  • Fellowship: Stanford University Rheumatology Fellowship (2016) CA
  • Board Certification: American Board of Internal Medicine, Rheumatology (2016)
  • Residency: Massachusetts General Hospital Internal Medicine Residency (2014) MA
  • Medical Education: Harvard Medical School (2011) MA
  • Bachelor of Arts, Pomona College (2004)

Research & Scholarship

Clinical Trials


  • Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors Recruiting

    This study (contRAst 3 [202018: NCT04134728]) is a Phase 3, randomized, multicenter, double-blind study to assess the safety and efficacy of GSK3196165 in combination with conventional (cs) DMARD[s]) or the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to biologic (b) DMARD[s]) and/or JAK inhibitors. The study will consist of a screening phase of up to 6 weeks followed by 24 week treatment phase in which participants will be randomized in ratio of 6:6:6:1:1:1 to GSK3196165 150 milligrams (mg) subcutaneously (SC) weekly,GSK3196165 90 mg SC weekly, sarilumab 200 mg SC every other week or placebo (three arms) respectively, all in combination with background csDMARD(s). At Week 12, participants in the three placebo arms will switch from placebo to active intervention (either GSK3196165 150 mg SC weekly, GSK3196165 90 mg SC weekly, or sarilumab 200 mg SC every other week). Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study (contRAst X [209564: NCT04333147]). Any participant who does not transition into study 209564 will undergo a safety follow-up visit at Week 34 (corresponding to 12 weeks after the last potential dose of sarilumab, at Week 22).

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  • Open Label Two-Arm Study to Evaluate Rilzabrutinib (PRN1008) in IgG4-Related Disease Patients Recruiting

    PRN1008-017 is a Phase 2a, multi-center, open-label, two-arm study of approximately 25 patients with active IgG4-related disease (IgG4-RD). The two arms include (1) Experimental: PRN1008 with glucocorticoids and (2) Active Comparator: glucocorticoids only.

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  • Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis Recruiting

    The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.

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  • A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE Not Recruiting

    To compare the effect of RAYOS versus immediate-release (IR) prednisone on fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

    Stanford is currently not accepting patients for this trial. For more information, please contact Mark Genovese, 650-498-5630.

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  • A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug Not Recruiting

    This is a Phase 3 multicenter study that includes two periods. Period 1 is designed to compare the safety, tolerability, and efficacy of ABT-494 Dose A once daily (QD) and Dose B QD versus placebo in participants with moderately to severely active Psoriatic Arthritis (PsA) who have an inadequate response to Biological Disease Modifying Anti-Rheumatic Drug (bDMARDs). Period 2 evaluates the safety, tolerability and efficacy of ABT-494 Dose A QD and Dose B QD in subjects with PsA who have completed Period 1.

    Stanford is currently not accepting patients for this trial.

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  • A Study of Inebilizumab Efficacy and Safety in IgG4- Related Disease Not Recruiting

    This study aims to define the efficacy and safety of inebilizumab for the prevention of flare of IgG4-related disease (IgG4-RD).

    Stanford is currently not accepting patients for this trial.

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  • BAFF/IL-17 Bispecific Antibody Treatment in Subjects With Primary Sjogren's Syndrome Not Recruiting

    To demonstrate that tibulizumab (LY3090106) treatment improves the mean unstimulated salivary flow rate or the salivary gland total ultrasound score (TUS) in primary Sjogren's syndrome patients at week 12 compared to the baseline visit.

    Stanford is currently not accepting patients for this trial.

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  • Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) Not Recruiting

    RA is a chronic, systemic inflammatory autoimmune disease which requires treatment for a long time period, hence it is important to study the long-term safety and efficacy of the continuous treatment with GSK3196165 over several years. This is a Phase 3, multicenter, parallel group treatment and long-term extension study primarily to assess safety with efficacy assessment as a secondary objective. Adult participants with RA who have completed the treatment phase of a qualifying GSK3196165 clinical studies (Phase 3 studies contRAst 1 (201790: NCT03980483), contRAst 2 (201791: NCT03970837) and contRAst 3 (202018: NCT04134728) and who, in investigator's judgement will benefit from extended treatment with GSK3196165 will be included in this study (contRAst X [209564: NCT04333147]). Participants will continue to receive the same background conventional synthetic disease modifying anti-rheumatic drug(s) [csDMARD(s)] treatment as they received in their qualifying study. Eligible participants will be enrolled to receive weekly GSK3196165 90 milligrams (mg) or 150 mg by subcutaneous (SC) injection. The anticipated study duration is approximately 4 years which will enable participants to receive treatment with GSK3196165 until it is expected to become commercially available. Approximately 3000 participants from the qualifying studies will participate in this long-term extension study.

    Stanford is currently not accepting patients for this trial.

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  • Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN) Not Recruiting

    The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (previously GS-9876) in adults with lupus membranous nephropathy (LMN).

    Stanford is currently not accepting patients for this trial. For more information, please contact Matthew Baker, 650-498-5630.

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  • Zanubrutinib in Patients With IgG4-Related Disease Not Recruiting

    The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease

    Stanford is currently not accepting patients for this trial.

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Lab Affiliations


Publications

All Publications


  • Comparison of Adverse Events Among Home- vs Facility-Administered Biologic Infusions, 2007-2017. JAMA network open Baker, M. C., Weng, Y., Fairchild, R., Ahuja, N., Rohatgi, N. 2021; 4 (6): e2110268

    Abstract

    Importance: Infusion reactions occur in 7% to 20% of patients receiving biologics. Home infusions are convenient and incur lower costs but may be associated with more adverse events; the safety of receiving biologic infusions for immune-mediated diseases at home remains unclear.Objective: To assess whether patients receiving home biologic infusions have increased adverse events requiring emergency department (ED) or hospital admission compared with patients receiving facility infusions.Design, Setting, and Participants: This retrospective cohort study used administrative claims data from a large national insurer for adult patients who received biologic infusions for immune-mediated disease between January 2007 and December 2017. Patients with hematologic malignant neoplasms or bone marrow transplantation were excluded. Data were analyzed from August 2019 to October 2020.Main Outcomes and Measures: ED or hospital admission on the same or next day after administration of a biologic infusion at home vs at a facility; secondary outcomes included discontinuation of the biologic after an ED or hospital admission and postinfusion mortality.Results: Of a total of 57?220 patients (mean [SD] age, 50.1 [14.8] years; 512?314 [68.1%] women) who received 752?150 biologic infusions (34?078 home infusions [4.5%] to 3954 patients and 718?072 facility infusions [95.5%] to 54?770 patients), patients who received home infusions were younger (mean [SD] age, 43.2 [13.2] vs 51.3 [14.8] years), more likely to be men (14?031 [41.2%] vs 225?668 [31.4%]), and had a lower Charlson comorbidity score compared with patients who received facility infusions (mean [SD] score, 0.5 [1.0] vs 1.1 [1.3]). Home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after the infusion (odds ratio [OR], 1.25; 95% CI, 1.09-1.44; P=.002) and 28% increased odds of discontinuation of the biologic after the ED or hospital admission (OR, 1.28; 95% CI, 1.08-1.51; P=.005). There was no difference in postinfusion mortality between home or facility infusions. The rates of adverse events were highest with home infusions of tocilizumab (48 of 481 infusions [10.0%]), vedolizumab (150 of 2681 infusions [5.6%]), and infliximab (1085 of 20?653 infusions [5.3%]), although the number of tocilizumab and vedolizumab infusions was low.Conclusions and Relevance: In this study, biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care. Because the number of home infusions has increased and is expected to continue to rise, the safety implications of administering biologic infusions at home needs to be further assessed.

    View details for DOI 10.1001/jamanetworkopen.2021.10268

    View details for PubMedID 34081140

  • Neutralizing Anti-Interleukin-1 Receptor-Antagonist Autoantibodies Induce Inflammatory and Fibrotic Mediators in IgG4-Related Disease. The Journal of allergy and clinical immunology Jarrell, J. A., Baker, M. C., Perugino, C. A., Liu, H., Bloom, M. S., Maehara, T., Wong, H. H., Lanz, T., Adamska, J. Z., Kongpachith, S., Sokolove, J., Stone, J. H., Pillai, S. S., Robinson, W. H. 2021

    Abstract

    BACKGROUND: IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition involving loss of B cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined.OBJECTIVE: To identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD.METHODS: We sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative monoclonal antibodies (mAb) were expressed and their specificities characterized using cytokine microarrays. The role of anti-interleukin-1 receptor-antagonist (IL-1RA) autoantibodies was investigated using in vitro assays.RESULTS: We identified strong reactivity against human IL-1RA using a clonally-expanded plasmablast-derived mAb from a patient with IgG4-RD. IgG4-RD patient plasma exhibited elevated levels of reactivity against IL-1RA compared to controls and neutralized IL-1RA activity, resulting in inflammatory and fibrotic mediator production in vitro. IL-1RA was detected in lesional tissues from IgG4-RD patients. Patients with anti-IL-1RA autoantibodies of the IgG4 subclass had greater numbers of organs affected than those without anti-IL-1RA autoantibodies. Peptide analyses identified IL-1RA epitopes targeted by anti-IL-1RA antibodies at sites near the IL-1RA/IL-1R interface. Serum from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also had elevated levels of anti-IL-1RA autoantibodies compared to controls.CONCLUSION: A subset of patients with IgG4-RD have anti-IL-1RA autoantibodies, which promote pro-inflammatory and pro-fibrotic meditator production via IL-1RA neutralization. These findings support a novel immunological mechanism underlying the pathogenesis of IgG4-RD. Anti-IL-1RA autoantibodies are also present in a subset of patients with SLE and RA, suggesting a potential common pathway in multiple autoimmune diseases.

    View details for DOI 10.1016/j.jaci.2021.05.002

    View details for PubMedID 33974929

  • Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study LANCET RHEUMATOLOGY Marsal, S., Corominas, H., Jose de Agustin, J., Perez-Garcia, C., Lopez-Lasanta, M., Borrell, H., Reina, D., Sanmarti, R., Narvaez, J., Franco-Jarava, C., Peterfy, C., Antonio Narvaez, J., Sharma, V., Alataris, K., Genovese, M. C., Baker, M. C. 2021; 3 (4): E262-E269
  • Non-invasive Vagus Nerve Stimulation Improves Signs and Symptoms of Rheumatoid Arthritis: Results of a Pilot Study Marsal, S., Corominas, H., De Agustin De Oro, J., Perez Garcia, C., Lopez Lasanta, M., Borrell, H., Reina, D., Sanmarti, R., Javier Narvaez, F., Franco-Jarava, C., Peterfy, C., Antonio Narvaez, J., Sharma, V., Alataris, K., Genovese, M., Baker, M. WILEY. 2020
  • CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. Frontiers in immunology Bhamidipati, K. n., Silberstein, J. L., Chaichian, Y. n., Baker, M. C., Lanz, T. V., Zia, A. n., Rasheed, Y. S., Cochran, J. R., Robinson, W. H. 2020; 11: 626820

    Abstract

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In healthy donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.

    View details for DOI 10.3389/fimmu.2020.626820

    View details for PubMedID 33658999

    View details for PubMedCentralID PMC7917337

  • A Mortality Risk Score Model for Clinically Amyopathic Dermatomyositis-Associated Interstitial Lung Disease: Will It Have the Necessary "FLAIR" to Improve Clinical Outcomes? Chest Baker, M. C., Chung, L. n., Fiorentino, D. F. 2020; 158 (4): 1307?9

    View details for DOI 10.1016/j.chest.2020.06.001

    View details for PubMedID 33036075

  • Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD open Baker, M. n., Chaichian, Y. n., Genovese, M. n., Derebail, V. n., Rao, P. n., Chatham, W. n., Bubb, M. n., Lim, S. n., Hajian, H. n., Gurtovaya, O. n., Patel, U. n., Tumlin, J. n. 2020; 6 (3)

    Abstract

    Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16.Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib.The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.NCT03285711.

    View details for DOI 10.1136/rmdopen-2020-001490

    View details for PubMedID 33380521

  • Osteoarthritis risk is reduced after treatment with ticagrelor compared to clopidogrel: a propensity score matching analysis. Arthritis & rheumatology (Hoboken, N.J.) Baker, M. C., Weng, Y. n., William, R. H., Ahuja, N. n., Rohatgi, N. n. 2020

    Abstract

    Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has anti-inflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine. The aim of this study was to determine whether treatment with ticagrelor was associated with a lower risk of OA.We conducted a 1:2 propensity score matching analysis using the Optum Clinformatics? Data Mart from 2011 to 2017. We included patients who received either ticagrelor or clopidogrel for at least 90 days and excluded those with a prior diagnosis of OA or inflammatory arthritis. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel.Our propensity score matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days on treatment of 287 and 284 respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox-regression analysis estimated a hazard ratio of 0.71 (95% CI 0.64-0.79, p<0.001) for developing OA after treatment with ticagrelor compared to clopidogrel.Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to clopidogrel over five years of follow-up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine.

    View details for DOI 10.1002/art.41412

    View details for PubMedID 32564514

  • Dermatomyositis Associated With a Skull Base Chondrosarcoma JCR-JOURNAL OF CLINICAL RHEUMATOLOGY Baker, M. C., Smith, G. P., Miloslavsky, E. M. 2019; 25 (4): E50?E53
  • TNF-alpha inhibition for the treatment of cardiac sarcoidosis. Seminars in arthritis and rheumatism Baker, M. C., Sheth, K. n., Witteles, R. n., Genovese, M. C., Shoor, S. n., Simard, J. F. 2019

    Abstract

    Tumor necrosis factor alpha (TNF-?) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking.We conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes.We identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-? inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-? inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use.A large cohort (n=77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n=20) received TNF-? inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-? inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

    View details for DOI 10.1016/j.semarthrit.2019.11.004

    View details for PubMedID 31806154

  • Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance PLOS ONE Kramer, D. B., Baker, M., Ransford, B., Molina-Markham, A., Stewart, Q., Fu, K., Reynolds, M. R. 2012; 7 (7)

    Abstract

    Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting.We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices.Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism.Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.

    View details for DOI 10.1371/journal.pone.0040200

    View details for Web of Science ID 000306956300012

    View details for PubMedID 22829874

    View details for PubMedCentralID PMC3400651

  • Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen BLOOD Leitner, W. W., Baker, M. C., Berenberg, T. L., Lu, M. C., Yannie, P. J., Udey, M. C. 2009; 113 (1): 37-45

    Abstract

    Nucleic acid-based vaccines are effective in infectious disease models but have yielded disappointing results in tumor models when tumor-associated self-antigens are used. Incorporation of helper epitopes from foreign antigens into tumor vaccines might enhance the immunogenicity of DNA vaccines without increasing toxicity. However, generation of fusion constructs encoding both tumor and helper antigens may be difficult, and resulting proteins have unpredictable physical and immunologic properties. Furthermore, simultaneous production of equal amounts of highly immunogenic helper and weakly immunogenic tumor antigens in situ could favor development of responses against the helper antigen rather than the antigen of interest. We assessed the ability of 2 helper antigens (beta-galactosidase or fragment C of tetanus toxin) encoded by one plasmid to augment responses to a self-antigen (lymphoma-associated T-cell receptor) encoded by a separate plasmid after codelivery into skin by gene gun. This approach allowed adjustment of the relative ratios of helper and tumor antigen plasmids to optimize helper effects. Incorporation of threshold (minimally immunogenic) amounts of helper antigen plasmid into a DNA vaccine regimen dramatically increased T cell-dependent protective immunity initiated by plasmid-encoded tumor-associated T-cell receptor antigen. This simple strategy can easily be incorporated into future vaccine trials in experimental animals and possibly in humans.

    View details for DOI 10.1182/blood-2008-01-136267

    View details for Web of Science ID 000262162800010

    View details for PubMedID 18832136

    View details for PubMedCentralID PMC2614641

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