Meet the Expert: Charles G. Drake, MD, PhD Associate Professor, Oncology, Immunology and Urology Johns Hopkins University School of Medicine Baltimore, MD USA
Charles Drake received his PhD in Immunology from the National Jewish Center for Immunology and his MD from the University of Colorado Health Sciences Center. After completing an internal medicine residency on the Osler medicine service at Johns Hopkins, he entered the field of medical oncology. During Dr. Drake’s oncology fellowship, he began to investigate the immune response to prostate cancer, developing a unique murine model to perform studies on antigen-specific T-cell tolerance to tumors. Experiments in this model supported the concept that androgen-ablation could mitigate tolerance to prostate cancer, creating a window during which tumor vaccination could prove successful (Cancer Cell 2005).
Currently, Dr. Drake is the co-director of the Multidisciplinary Prostate Cancer Clinic at Hopkins, where the combination of androgen-ablation and vaccination is being examined in a translational, pre-surgical trial. Using additional in vivo models, the Drake laboratory showed that LAG-3 is relatively over-expressed on non-functional T cells, and that LAG-3 blockade affects T-cell function in both Treg-dependent and Treg-independent mechanisms (JCI 2007). More recently, the laboratory was able to show that blocking the immune checkpoints PD-1 and LAG-3 could prove synergistic, in several in vivo cancer models. Ongoing work in the laboratory is focused on understanding the role of LAG-3 in regulatory T-cell induction, as well as the regulation of immune checkpoint molecules and ligands in prostate and kidney cancer.
Areas of Clinical Expertise:
Professional Memberships and Awards:
1997-1999 Member, American College of Physicians
2000-present Member, American Society of Clinical Oncology (ASCO)
2001-present Member, American Association for Cancer Research (AACR)
2010-present Member, American Association of Immunology (AAI)
Drake CG, Babcock SK, Palmer E, Kotzin BL. Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. Proc Natl Acad Sci U S A. 1994;91(9):4062-6. PMCID: 43723.
Rozzo SJ, Drake CG, Chiang BL, Gershwin ME, Kotzin BL. Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus. J Immunol. 1994;153(3):1340-51.
Drake CG, Rozzo SJ, Hirschfeld HF, Smarnworawong NP, Palmer E, Kotzin BL. Analysis of the New Zealand Black contribution to lupus-like renal disease. Multiple genes that operate in a threshold manner. J Immunol. 1995;154(5):2441-7.
Rozzo SJ, Vyse TJ, Drake CG, Kotzin BL. Effect of genetic background on the contribution of New Zealand Black loci to autoimmune lupus nephritis. P Natl Acad Sci USA. 1996;93(26):15164-8. PMCID: 26374.
Drake CG, Rozzo SJ, Vyse TJ, Kotzin BL. Absence of coding sequence polymorphism in the serum amyloid P component gene (Sap) in autoimmune New Zealand black mice. Mamm Genome. 1996;7(6):466-7.
Vyse TJ, Drake CG, Rozzo SJ, Roper E, Izui S, Kotzin BL. Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice. J Clin Invest. 1996;98(8):1762-72. PMCID: 507614.
Vyse TJ, Rozzo SJ, Drake CG, Izui S, Kotzin BL. Control of multiple autoantibodies linked with a lupus nephritis susceptibility locus in New Zealand Black mice. Journal of Immunology. 1997;158(11):5566-74.
Vyse TJ, Rozzo SJ, Drake CG, Appel VB, Lemeur M, Izui S, Palmer E, Kotzin BL. Contributions of Ea(z) and Eb(z) MHC genes to lupus susceptibility in New Zealand mice. Journal of Immunology. 1998;160(6):2757-66.
Huang CT, Huso DL, Lu ZB, Wang TH, Zhou G, Kennedy EP, Drake CG, Morgan DJ, Sherman LA, Higgins AD, Pardoll DM, Adler AJ. CD4(+) T cells pass through an effector phase during the process of in vivo tolerance induction. Journal of Immunology. 2003;170(8):3945-53.
Kowalski J, Drake C, Schwartz RH, Powell J. Non-parametric, hypothesis-based analysis of microarrays for comparison of several phenotypes. Bioinformatics. 2004;20(3):364-73.
Doody ADH, Kovalchin JT, Mihalyo MA, Hagymasi AT, Drake CG, Adler AJ. Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8(+) T cell effector function. Journal of Immunology. 2004;172(10):6087-92. PMCID: 2846363.
Huang CT, Workman CJ, Flies D, Pan XY, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DAA. Role of LAG-3 in regulatory T cells. Immunity. 2004;21(4):503-13.
Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Drake CG, Hipkiss EL, Tatsumi M, Dang LH, Diaz LA, Jr., Pomper M, Abusedera M, Wahl RL, Kinzler KW, Zhou S, Huso DL, Vogelstein B. Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proc Natl Acad Sci U S A. 2004;101(42):15172-7. PMCID: 523456.
Drake CG, Doody AD, Mihalyo MA, Huang CT, Kelleher E, Ravi S, Hipkiss EL, Flies DB, Kennedy EP, Long M, McGary PW, Coryell L, Nelson WG, Pardoll DM, Adler AJ. Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell. 2005;7(3):239-49. PMCID: 2846360.
Hurchla MA, Sedy JR, Gavrieli M, Drake CG, Murphy TL, Murphy KM. B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells. J Immunol. 2005;174(6):3377-85.
Safford M, Collins S, Lutz MA, Allen A, Huang CT, Kowalski J, Blackford A, Horton MR, Drake C, Schwartz RH, Powell JD. Egr-2 and Egr-3 are negative regulators of T cell activation. Nat Immunol. 2005;6(5):472-80.
Palapattu GS, Meeker A, Harris T, Collector MI, Sharkis SJ, DeMarzo AM, Warlick C, Drake CG, Nelson WG. Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium. J Urol. 2006;176(2):813-8.
Collins S, Wolfraim LA, Drake CG, Horton MR, Powell JD. Cutting Edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription. J Immunol. 2006;177(12):8301-5.
Zhou G, Drake CG, Levitsky HI. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood. 2006;107(2):628-36. PMCID: 1895618.
Litvinov IV, Vander Griend DJ, Antony L, Dalrymple S, De Marzo AM, Drake CG, Isaacs JT. Androgen receptor as a licensing factor for DNA replication in androgen-sensitive prostate cancer cells. Proc Natl Acad Sci U S A. 2006;103(41):15085-90. PMCID: 1622781.
Goldberg MV, Maris CH, Hipkiss EL, Flies AS, Zhen L, Tuder RM, Grosso JF, Harris TJ, Getnet D, Whartenby KA, Brockstedt DG, Dubensky TW, Jr., Chen L, Pardoll DM, Drake CG. Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood. 2007;110(1):186-92. PMCID: 1896112.
Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, Anders R, Netto G, Getnet D, Bruno TC, Goldberg MV, Pardoll DM, Drake CG. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 2007;117(11):3383-92. PMCID: 2000807.
Harris TJ, Grosso JF, Yen HR, Xin H, Kortylewski M, Albesiano E, Hipkiss EL, Getnet D, Goldberg MV, Maris CH, Housseau F, Yu H, Pardoll DM, Drake CG. Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol. 2007;179(7):4313-7.
Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG, Powell JD. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood. 2008;111(1):251-9. PMCID: 2200810.
Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res. 2008;14(11):3254-61. PMCID: 3082357.
Harris TJ, Hipkiss EL, Borzillary S, Wada S, Grosso JF, Yen HR, Getnet D, Bruno TC, Goldberg MV, Pardoll DM, DeWeese TL, Drake CG. Radiotherapy augments the immune response to prostate cancer in a time-dependent manner. Prostate. 2008;68(12):1319-29. PMCID: 2710770.
Getnet D, Maris CH, Hipkiss EL, Grosso JF, Harris TJ, Yen HR, Bruno TC, Wada S, Adler A, Georgantas RW, Jie C, Goldberg MV, Pardoll DM, Drake CG. Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. J Immunol. 2009;182(8):4675-85. PMCID: 3082355.
Levy MY, Sidana A, Chowdhury WH, Solomon SB, Drake CG, Rodriguez R, Fuchs EJ. Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation. J Pharmacol Exp Ther. 2009;330(2):596-601. PMCID: 2713091.
Pan F, Yu H, Dang EV, Barbi J, Pan X, Grosso JF, Jinasena D, Sharma SM, McCadden EM, Getnet D, Drake CG, Liu JO, Ostrowski MC, Pardoll DM. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science. 2009;325(5944):1142-6. PMCID: 2859703.
Yen HR, Harris TJ, Wada S, Grosso JF, Getnet D, Goldberg MV, Liang KL, Bruno TC, Pyle KJ, Chan SL, Anders RA, Trimble CL, Adler AJ, Lin TY, Pardoll DM, Huang CT, Drake CG. Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol. 2009;183(11):7161-8. PMCID: 3082359.
Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 2009;15(2):114-23. PMCID: 2673504.
Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG, Vignali DA. LAG-3 regulates plasmacytoid dendritic cell homeostasis. J Immunol. 2009;182(4):1885-91. PMCID: 2675170.
Wang MH, Helzlsouer KJ, Smith MW, Hoffman-Bolton JA, Clipp SL, Grinberg V, De Marzo AM, Isaacs WB, Drake CG, Shugart YY, Platz EA. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate. 2009;69(8):874-85. PMCID: 3016874.
Grosso JF, Goldberg MV, Getnet D, Bruno TC, Yen HR, Pyle KJ, Hipkiss E, Vignali DA, Pardoll DM, Drake CG. Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells. J Immunol. 2009;182(11):6659-69. PMCID: 3082361.
Wada S, Yoshimura K, Hipkiss EL, Harris TJ, Yen HR, Goldberg MV, Grosso JF, Getnet D, Demarzo AM, Netto GJ, Anders R, Pardoll DM, Drake CG. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res. 2009;69(10):4309-18. PMCID: 3084614.
Sfanos KS, Bruno TC, Meeker AK, De Marzo AM, Isaacs WB, Drake CG. Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate. 2009;69(15):1694-703. PMCID: 2782577.
Azuma T, Zhu G, Xu H, Rietz AC, Drake CG, Matteson EL, Chen L. Potential role of decoy B7-H4 in the pathogenesis of rheumatoid arthritis: a mouse model informed by clinical data. PLoS Med. 2009;6(10):e1000166. PMCID: 2760136.
Getnet D, Grosso JF, Goldberg MV, Harris TJ, Yen HR, Bruno TC, Durham NM, Hipkiss EL, Pyle KJ, Wada S, Pan F, Pardoll DM, Drake CG. A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol Immunol. 2010;47(7-8):1595-600. PMCID: 3060613.
Hsu DS, Kim MK, Balakumaran BS, Acharya CR, Anders CK, Clay T, Lyerly HK, Drake CG, Morse MA, Febbo PG. Immune signatures predict prognosis in localized cancer. Cancer Invest. 2010;28(7):765-73. PMCID: Not supported through NIH funding.
Radojcic V, Pletneva MA, Yen HR, Ivcevic S, Panoskaltsis-Mortari A, Gilliam AC, Drake CG, Blazar BR, Luznik L. STAT3 signaling in CD4+ T cells is critical for the pathogenesis of chronic sclerodermatous graft-versus-host disease in a murine model. J Immunol. 2010;184(2):764-74. PMCID: 2941975.
Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167-75. PMCID: Not supported through NIH funding.
Platz EA, Sutcliffe S, De Marzo AM, Drake CG, Rifai N, Hsing AW, Hoque A, Neuhouser ML, Goodman PJ, Kristal AR. Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies. Cancer Causes Control. 2010;21(6):847-51. PMCID: 3010861.
Woo SR, Li N, Bruno TC, Forbes K, Brown S, Workman C, Drake CG, Vignali DA. Differential subcellular localization of the regulatory T-cell protein LAG-3 and the coreceptor CD4. Eur J Immunol. 2010;40(6):1768-77. PMCID: 2987677.
Keizman D, Zahurak M, Sinibaldi V, Carducci M, Denmeade S, Drake C, Pili R, Antonarakis ES, Hudock S, Eisenberger M. Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: results of a phase I/II double-blinded, randomized study. Clin Cancer Res. 2010;16(21):5269-76. PMCID: PMC3444815
Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X, Drake CG, Korman AJ, Vignali DA. Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. J Immunol. 2011;187(7):3493-8. PMCID: 3178660.
Dalai SK, Khoruzhenko S, Drake CG, Jie CC, Sadegh-Nasseri S. Resolution of infection promotes a state of dormancy and long survival of CD4 memory T cells. Immunol Cell Biol. 2011;89(8):870-81. PMCID: 3131418.
Collison LW, Delgoffe GM, Guy CS, Vignali KM, Chaturvedi V, Fairweather D, Satoskar AR, Garcia KC, Hunter CA, Drake CG, Murray PJ, Vignali DA. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012;13(3):290-9.
Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, Tangsombatvisit S, Grosso JF, Netto G, Smeltzer MP, Chaux A, Utz PJ, Workman CJ, Pardoll DM, Korman AJ, Drake CG*, and, Vignali DA*, (*contributed equally). Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T cell function to promote tumoral immune escape. Cancer Res. 2012;72(4):917-27. PMCID:PMC3288154
Zabransky DJ, Smith HA, Thoburn CJ, Zahurak M, Keizman D, Carducci M, Eisenberger MA, McNeel DG, Drake CG, Antonarakis ES. Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer. Prostate. 2012;72(5):487-98. PMCID: 21748755.
Bruno TC, Rothwell C, Grosso JF, Getnet D, Yen HR, Durham NM, Netto G, Pardoll DM, Drake CG. Anti-tumor effects of endogenous prostate cancer-specific CD8 T cells in a murine TCR transgenic model. Prostate. 2012;72(5):514-22. PMCID: 21761425.
Zabransky DJ, Nirschl CJ, Durham NM, Park BV, Ceccato CM, Bruno TC, Tam AJ, Getnet D, Drake CG. Phenotypic and functional properties of Helios+ regulatory T cells. PLoS One. 2012;7(3):e34547. PMCID: 3316700.
Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer. N Engl J Med. 2012.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. N Engl J Med. 2012.
Dluzniewski PJ, Wang MH, Zheng SL, De Marzo AM, Drake CG, Fedor HL, Partin AW, Han M, Fallin MD, Xu J, Issacs WB, Platz EA. Variation in IL10 and Other Genes Involved in the Immune Response and in Oxidation and Prostate Cancer Recurrence. Cancer Epidemiol Biomarkers. Epub Aug 2, 2012. PMCID:PMC3467312
Olmos D, Brewer D, Clark J, Danila DC, Parker C, Attard G, Fleisher M, Reid AH, Castro E, Sandhu SK, Barwell L, Oommen NB, Carreira S, Drake CG, Jones R, Cooper CS, Scher HI, de Bono JS. Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study. Lancet Oncol 2012:11:1114-24. PMID: 23059046.
Jackson CM, Flies DB, Mosse CA, Parwani A, Hipkiss EL, Drake CG. Strain-specific induction of experimental autoimmune prostatitis in mice. Prostate. 2012: Epub 11/5. PMID 23129407.
Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, Xu H, Yao S, Pons A, Chen L, Pardoll DM, Brahmer JR, Topalian SL. Durable cancer regression off treatment and effective re-induction therapy with an anti-PD-1 antibody. Clin Cancer Res. 2012, Epub 11/20. PMID 23169436
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BACKGROUND: Perioperative cisplatin combination chemotherapy is associated with a survival benefit in patients with invasive bladder cancer (BCa). However, in a recent report from the National Cancer Database (NCDB), only 11.6% of stage III BCa patients received perioperative chemotherapy, the majority in the adjuvant setting.
PURPOSE: Appropriate use of adjuvant chemotherapy is a widely recognized quality measure of colorectal cancer care. The objective of this study was to test the hypothesis that surgical complications are associated with omission of chemotherapy for colorectal cancer.
PURPOSE: Mounting evidence suggests a relationship between hospital volume and outcomes after major cancer surgery; however, the absolute benefits of volume-based referral on a national basis are unclear.
CONTEXT: Muscle-invasive bladder cancer (MIBC) is a disease with a pattern of predominantly distant and early recurrences. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved outcomes for MIBC. OBJECTIVE: To review the data supporting perioperative chemotherapy and emerging regimens for MIBC.
BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy.