Director, Center for Protein Therapeutics with research focusing on the utilization of pharmacokinetic and pharmacodynamic analyses and mathematical modeling to guide the discovery and development of new immunotherapies for cancer and autoimmunity.
Research Interests and Projects:
1. Development of antibody conjugates for targeted, intra-cellular delivery of macromolecular toxins
2. Engineering monoclonal antibodies for improved pharmacokinetic properties
3. Investigation of sources of inter-individual variability in monoclonal antibody pharmacokinetics
4. Investigation of strategies to overcome the "binding site barrier" to antibody distribution in solid tumors
5. Development of improved mathematical models for predicting the disposition and effects of monoclonal antibody drugs
6. Development of new targeting strategies to optimize the safety and efficacy of intraperitoneal chemotherapy of ovarian cancers (CA118213)
7. Development of FcRn inhibitors for treatment of humoral autoimmune diseases (e.g., myasthenia gravis, autoimmune neutropenia) (AI60687)
8. Development of new strategies to treat immune thrombocytopenic purpura (HL67347)
9. Investigation of the role of FcRn in the absorption, distribution, and elimination of IgG antibodies
10. Development of antibody-based therapies to treat and prevent infection. Efforts are currently focused on prevention of infection by Treponema denticola (DE023080), S. aureus, and A. baumannii
Education and Training:
PhD, State University of New York at Buffalo (1996)
BS, State University of New York at Buffalo (1991)
Employment:
Associate Dean for Research, SPPS, University at Buffalo, School of Pharmacy and Pharamceutical Sciences (2011-present)
Professor, Pharmaceutical Sciences, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences (2008-present)
Associate Professor, Pharmaceutical Sciences, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences (2003–2008)
Assistant Professor, Pharmaceutical Sciences, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences (1999–2003)
Assistant Professor, Pharmaceutics and Pharmaceutical Chemistry, University of Utah, College of Pharmacy (1997–1999)
Clinical Assistant Professor, Pharmaceutics, University at Buffalo, School of Pharmacy (1996–1997)
Awards and Honors:
BIOMED Lecturer (2012)
Elected AAPS Fellow (2010)
UNC / Eisai Distinguished Lecturer in Drug Delivery (2010)
Outstanding Manuscript in Modeling and Simulation (2009)
University at Buffalo, Top 100 Federal Grantee, 2005 (2005)
University at Buffalo, Young Investigator Achievement Award (2002)
University at Buffalo, Top 100 Federal Grantee (2002)
AAPS PPDM Annual Meeting Travel Award (2001)
AACP New Investigator Award (1999)
AACP New Investigator Award (1998)
University of Utah, College of Pharmacy Distinguished Teaching Award (1998)
AACP New Investigator Award (1997)
AAPS / Eli Lilly Graduate Symposium Award (1995)
AFPE Pre-doctoral Fellowship
New York State Regents Scholarship
Western New York Science Congress, Bronze Medal
Rho-Chi Honor Society
Schering-Plough Pre-doctoral Fellowship
SUNY at Buffalo Department of Pharmaceutics Graduate Scholar Award
SUNY at Buffalo School of Pharmacy Scholarship
Research Expertise:
Monoclonal Antibodies: Experienced in the development, production, purification, and PKPD characterization of monoclonal antibody drugs.
Ovarian Cancer Chemotherapy: A main objective of our research is to improve the safety and efficacy of ovarian cancer chemotherapy. Two main strategies are under investigation.
Develop mathematical models capable of characterizing the tremendous protocol-dependencies often observed in relationships between chemotherapeutic dosing and selectivity. Computer simulations are then utilized to predict optimal dosing strategies for the treatment of individuals.
Utilizes anti-drug antibodies to alter the distribution and elimination kinetics of chemotherapeutics as a means to provide targeted drug therapy of peritoneal metastases of ovarian cancer.
Our approach combines intraperitoneal administration of antineoplastic agents with systemic administration of anti-drug antibodies. The presence of anti-drug antibodies in the systemic circulation leads to rapid binding of drug diffusing out of the peritoneum and entering the blood, thereby reducing the extravascular distribution of the chemotherapeutic.
Pharmacokinetic and Pharmacodynamic: The utilization of pharmacokinetic and pharmacodynamic analyses and mathematical modeling to develop and evaluate rational approaches of optimizing drug therapy.
Research Centers:
Center of Excellence in Bioinformatics and Life Sciences
UB 2020 Strategic Strengths:
Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
July 2013–June 2018 Exploring New Virulence factors of the Oral Spirochete Treponema denticola NIDCR, NIH Role: Co-Investigator
October 2015–September 2016 Physiologically-based modeling of IgG pharmacokinetics Center for Protein Therapeutics Role: Principal Investigator $100,000
October 2015–September 2016 Effects of Albumin Tag on Peptide Pharmacokinetics Center for Protein Therapeutics Role: Principal Investigator $100,000
June 2014–May 2016 Investigation of the utility of LC/MS for characterization of the plasma and tissue PK of a novel series of antiCEA monocolonal antibodies. Hoffmann-La Roche Inc Role: Principal Investigator
June 2011–May 2016 PTD-mediated protein or drug delivery for cancer therapy NIH/NCI Role: Co-Investigator
October 2014–September 2015 Physiologically-based pharmacokinetic (PBPK) modeling of IgG Center for Protein Therapeutics Role: Principal Investigator $100,000
October 2014–September 2015 Determinants of mAb brain distribution in mouse models of Alzheimer’s Disease: Investigation of FcRn binding and charge Center for Protein Therapuetics Role: Principal Investigator $100,000
October 2014–September 2015 Investigation of the effects of co-administered drugs on mAb pharmacokinetics Center for Protein Therapeutics Role: Principal Investigator $100,000
October 2013–September 2014 Investigation of FcRn expression in human ontogenesis Center for Protein Therapeutics Role: Principal Investigator $100,000
October 2013–September 2014 Investigation of the influence of systemic lupus erythematosus on monoclonal antibody elimination in a mouse model Center for Protein Therapeutics Role: Principal Investigator $100,000
October 2013–September 2014 Investigation of the influence of protein losing enteropathy on mAb pharmacokinetics Center for Protein Therapeutics Role: Principal Investigator $100,000
September 2007–May 2011 Pharmacology and Bioengineering of New Treatments of ITP NIH/NIHLBI Role: Principal Investigator
September 2006–August 2010 Pharmacokinetic strategies to optimize IP chemotherapy NIH/NCI Role: Co-Investigator
May 2004–April 2008 FcRn Inhibitors for Antibody-Mediated Immune Conditions NIH/NIAID Role: Principal Investigator
October 2006–September 2007 Voraxaze effects on methotrexate-induced weight loss in mice Protherics PLC Role: Principal Investigator
April 2001–March 2005 Pharmacology and bioengineering of new treatments of ITP NIHLBI Role: Principal Investigator
May 2003–April 2004 Humanization of anti-methotrexate monoclonal antibodies American Association of Colleges of Pharmacy Role: Co-Investigator $5,500
June 2002–May 2003 Pharmacology of adjuvants for inverse targeting Kapoor Foundation Role: Principal Investigator $20,000
October 1997–September 1998 Optimization of intraperitorneal chemotherapy through use of anti-drug antibody therapy Americal Association of Colleges of Pharmacy, NIP Role: Co-Investigator $12,500
June 1997–May 1998 Inverse targeting with anti-drug antibodies: A new approach of optimizing chemotherapy Parenteral Drug Association Role: Principal Investigator $20,000
Abuqayyas L; Balthasar JP. Pharmacokinetic mAb-mAb Interaction: Anti-VEGF mAb Decreases the Distribution of Anti-CEA mAb into Colorectal Tumor Xenografts.. AAPS Journal. 2012; 14.
Duan X; Dai L; Chen S; Balthasar JP; Qu J. Nano-scale liquid chromatography/mass spectrometry and on-the-fly orthogonal array optimization for quantification of therapeutic monoclonal antibodies and the application in preclinical analysis. Journal of Chromatography A. 2012; 1251.
Duan X; Abuqayyas L; Dai L; Balthasar JP; Qu J. High-throughput method development for sensitive, accurate, and reproducible quantification of therapeutic monoclonal antibodies in tissues using orthogonal array optimization and nano liquid chromatography/selected reaction monitoring mass spectrometry.. 2012.
Girish S; Han C; Berglund EG; Huang SM; Joshi A; Martin SW; Peterson MC; Zhang LK; Zhao H; Balthasar JP; Evers R; Zhou H; Klunk L. AAPS Workshop Report: Strategies to Address Therapeutic Protein-Drug Interactions during Clinical Development. AAPS J. 2011.
Shah DK; Veith J; Bernacki RJ; Balthasar JP. Evaluation of combined bevacizumab and intraperitoneal carboplatin or paclitaxel therapy in a mouse model of ovarian cancer.. Cancer Chemother Pharmacol. 2011.
Shah DK; Balthasar JP. Physiologically based pharmacokinetic model for topotecan in mice.. J Pharmacokinet Pharmacodyn. 2011.
Shin BS; Bulitta JB; Balthasar JP; Kim M; Choi Y; Yoo SD. Prediction of human pharmacokinetics and tissue distribution of apicidin, a potent histone deacetylase inhibitor, by physiologically based pharmacokinetic modeling.. Cancer Chemother Pharmacol. 2010.
Urva SR; Yang VC; Balthasar JP. Physiologically based pharmacokinetic model for T84.66, a monoclonal anti-CEA antibody. Journal of Pharmaceutical Sciences. 2010; 99.
Urva SR; Balthasar JP. Target mediated disposition of T84.66, a monoclonal anti-CEA antibody: Application in the detection of colorectal cancer xenografts. Mabs. 2010; 2.
Urva SR; Yang VC; Balthasar JP. Development and validation of an enzyme linked immunosobent assay for the quantification of carcinoembryonic antigen in mouse plasma. J Immunoassay Immunochem. 2009; 30.
Garg A; Balthasar JP. Investigation of the influence of FcRn on the distribution of IgG to the brain. AAPS Journal. 2009; 11.
Shah DK; Shin BS; Veith J; Toth K; Bernacki RJ; Balthasar JP. Use of an anti-vascular endothelial growth factor antibody in a pharmacokinetic strategy to increase the efficacy of intraperitoneal chemotherapy. 2009.
Shin BS; Yoon CH; Balthasar JP; Choi BY; Hong SH; Kim HJ; Lee JB; Hwang SW; Yoo SD. Prediction of drug bioavailability in humans using immobilized artificial membrane phosphatidylcholine column chromatography and in vitro hepatic metabolic clearance. 2009.
Urva SR; Shin BS; Yang VC; Balthasar JP. Sensitive high performance liquid chromatographic assay for assessment of doxorubicin pharmacokinetics in mouse plasma and tissues. 2009.
Chen J; Lu Q; Balthasar JP. Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice.. Journal of Pharmacokinetics and Pharmacodynamics. 2007; 34.
Garg A; Balthasar JP. Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice. J Pharmacokinetics and Pharmacodynamics. 2007; 34.
Deng R; Balthasar JP. Pharmacokinetic/pharmacodynamic modeling of IVIG effects in a murine model of immune thrombocytopenia. 2007.
Deng R; Balthasar JP. Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia. 2007.
Shin BS; Choi JW; Balthasar JP; Hong DK; Kim JJ; Yoo SD. Determination of roxatidine in human plasma by liquid chromatography/electrospray mass spectrometry and application to a clinical pharmacokinetic study. 2007.
Wang EQ, Balthasar JP, Fung HL. Pharmacodynamics of in vivo nitroglycerin tolerance in normal conscious rats: effects of dose and dosing protocol.. Pharm Res. 2004; 21(1).
Deng R; Balthasar JP. Immune Complex Therapies for Treatment of Immune Thrombocytopenia. Developmentof Antibody-Based Therapeutics. 2012.
Shin BS; Shah D; Balthasar JP. Pharmacodynamics. Preclinical Development Handbook: ADME and Biopharmaceutical Properties. 2008.
Chen J; Balthasar JP. Development and characterization of high-affinity anti-topotecan IgG and fab fragments. Handbook of Pharmaceutical Technology. 2007.
American Association of Phamaceutical Scientists (1992)
American Association of Colleges of Pharmacy
American Association of Pharmaceutical Scientists
American Society for Pharmacology and Experimental Therapeutics
American Association for the Advancement of Science; American Association for the Advancement of Science
American Society of Hematology; American Society of Hematology
Presentations:
"Application of PBPK Modeling to Predict Monoclonal Antibody Disposition in Plasma and Tissues in Mouse Models of Human Colorectal Cancer" AAPS National Biotechnology Conference, AAPS (2013)
"In pursuit of predictive models for mAb pharmacokinetics: Striving for progress through mechanistic studies" 2nd Annual Symposium on Biotechnology, European Drug Metabolism Discussion Group, European Drug Metabolism Discussion Group (2013)
"Investigation of Gelonin Pharmacokinetics in Mice with Use of a New Enzyme Linked Immunosorbent Assay" 2013 AAPS National Biotechnology Conference, AAPS (2013)
"Mechanistic Considerations for Assessing DDI Risks for ADCs" AAPS National Biotechnology Conference, AAPS (2013)
"The influence of nephropathy on mAb disposition in a mouse model of diabetic nephropathy." 2013 AAPS National Biotechnology Conference, AAPS (2013)
"Use of mechanistic studies and mathematical modeling to characterize and predict antibody distribution in tissues" CIHR Biological Therapeutics Training Program Symposium, Canadian Institutes of Health Research (2013)
"Pharmacokinetics of Proteins and Peptides" New Jersey Drug Metabolism Discussion Group Symposium on Models, Pharmacogenomics, and Pharmacokinetics, New Jersey Drug Metabolism Discussion Group (2013)
"Use of PKPD modeling in the development of new monoclonal antibodies for treatment and detection of disease" , University at Buffalo, School of Dental Medicine (2013)
"Physiologically- based pharmacokinetic modeling to expedite the development of targeted nano-therapies" 2012 Chinese Pharmaceutical Conference, Chinese Pharmaceutical Conference (2012)
"Characterization of the Kinetics of Therapeutic Antibody Immune Complexes In Vivo Using Blue Native Electrophoresis and Targeted Nano-LC/MS Analysis" 60th ASMS conference on Mass Spectrometry and Allied Topics, ASMS (2012)
"Application of PK/PD modeling to Guide the Development of New Immunotherapies" BIOMED, University of Leuven (KU Leuven) (2012)
"Overview of Antibody Pharmacokinetics" , Vaccinex (2012)
"Monoclonal Antibody Lecture Series" , University of Paris V (2012)
"Overview of Ongoing Research in the Center for Protein Therapeutics" , Roche (2012)
"Application of PKPD modeling to expedite the discovery and early development of novel drug therapies" Korean Society of Pharmaceutical Sciences and Technology, 41st Annual Meeting, KPST (2011)
"An academic view of therapeutic protein drug interactions" 17th North America Regional ISSX Meeting, ISSX (2011)
"Mechanistic considerations for drug-drug interactions with biologicals" Centocor Drug-Drug Interaction Symposium, Centocor (2011)
"Overview of the determinants of mAb clearance & methods for characterizing target mediated mAb disposition" , Roche (2011)
"Preclinical considerations for mAbs" Annual Meeting of the American Clinical College of Pharmacy, ACCP (2011)
"Application of PKPD modeling to estimate effective clinical doses of mAb" , MedImmune (2011)
"Antibody Pharmacokinetics" , Ferring (2011)
"Antibody Pharmacokinetics and Pharmacodynamics Lecture Series" , University at Buffalo (2011)
"Antibody Pharmacokinetics and Pharmacodynamics Lecture Series" , Amgen (2011)
"Translation of TMD from animals to humans: Where are we and what is our vision?" , Roche (2011)
"Unusual and unexpected PK behavior of mAbs: Examples and possible mechanisms" AAPS National Biotechnology Conference, AAPS (2011)
"Investigation of the influence of FcRn on the pharmacokinetics of monoclonal antibodies" , Abbott (2011)
"Antibody Lecture Series" , Pfizer (2011)
"Antibody Pharmacokinetics Lecture Series" , University of Paris V (2011)
"Applications of Imaging for Investigation of mAb Pharmacokinetics and Pharmacodynamics" , Roche (2011)
"Mechanistic Modeling of Monoclonal Antibodies: Applications in discovery and early development" AAPS Annual Meeting, AAPS (2010)
"Application of PKPD Modeling to Guide the Discovery and Early Development of mAbs" , UNC/Eisai Distinguished Lecture in Drug Delivery (2010)
"Strategies for Rational Optimization of mAb Bioavailability, Persistence, and Efficacy" , Eisai (2010)
"Investigation of the influence of FcRn on the pharmacokinetics of monoclonal antibodies" , Pfizer (2010)
"Monoclonal Antibodies: PK Questions and Applications of PKPD Modeling" , Bayer (2010)
"Antibody Pharmacokinetics" , NovoNordisk (2010)
"Pharmacokinetic strategies for improved cancer therapy and detection" , University of Kentucky (2010)
"Application of PKPD to assist in the development of immunotherapies" Twellfth Buffalo Pharmaceutics Symposium (2010)
"An academic view of protein drug-drug interactions" National Biotechnology Conference, American Association of Pharmaceutical Scientists (2010)
"Antibody pharmacokinetics and pharmacodynamics" Antibody pharmacokinetics and pharmacodynamics, Workshop, supported by attendees (2010)
"Predicting the Human Pharmacokinetics of Monoclonal Antibodies: Concepts and Examples" ISSX Annual Meeting, International Society for the Study of Xenobiotics (2010)
"SC Bioavailability of mAb: Investigations with Knockout Mice and Engineered mAb" AAPS National Biotechnology Conference, AAPS (2010)
"SC Bioavailability of mAb: Investigations with knockout mice and engineered mAb" National Biotechnology Conference, American Association of Pharmaceutical Scientists (2010)
"Scaling the Pharmacokinetics of Biologics Across Species" National Biotechnology Conference, American Association of Pharmaceutical Scientists (2010)
"Scaling the Pharmacokinetics of Biologics Across Species" AAPS National Biotechnology Conference, AAPS (2010)
"Antibody pharmacokinetics and pharmacodynamics" , Boerhinger-Ingelheim (2010)
"Antibody pharmacokinetics and pharmacodynamics" , Glaxo Smith Kline (2010)
"Antibody pharmacokinetics and pharmacodynamics" , Boerhinger-Ingelheim (2010)
"Drug-drug interactions with monoclonal antibodies" , Roche (2010)
"Effects of FcR on the Disposition of Monoclonal Antibodies" , Roche (2010)
"Physiologically-Based Pharmacokinetic Modeling of Monolonal Antibodies" , Roche (2010)
"Antibody pharmacokinetics and pharmacodynamics" , Schering-Plough (2009)
"Target mediated disposition of antibodies" , Abbott (2009)
"Pharmacology and Mechanisms of IVIG Action Emphasis on the Use of IVIG for ITP" American Association of Blood Banks National Meeting, American Association of Blood Banks (2009)
"Antibody pharmacokinetics and pharmacodynamics" , Merck (2009)
"Antibody pharmacokinetics and pharmacodynamics" , Roche (2009)
"Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies" Land O'Lakes Meeting, University of Wisconsin (2009)
"Application of PKPD M&S to Discovery/Development of Large Molecules: Learning from Antibodies" Gordon Conference on Drug Metabolism, Gordon Conference (2009)
"Antibody pharmacokinetics and pharmacodynamics" Antibody pharmacokinetics and pharmacodynamics, Workshop, supported by attendees (2009)
"Antibody pharmacokinetics and pharmacodynamics" , Pfizer (2009)
"Antibody pharmacokinetics and pharmacodynamics" , Glaxo Smith Kline (2009)
"Application of PKPD to guide the development of new immunotherapies for cancer" , Biogen Idec (2009)
"Several lectures were provided" Course on Pharmacokinetics and Pharmacodynamics, University of Paris (2009)
"Several lectures were provided" , Roche (2009)
"A Pharmacokinetic Strategy to Increase the Efficacy of Intraperitoneal Chemotherapy" AAPS Annual Meeting, AAPS (2008)
"Improving Therapeutic Benefits of Intraperitoneal Chemotherapy by Co-Administration of Anti-Angiogenic Therapy" AAPS Annual Meeting, AAPS (2008)
"Investigation of the Influence of Antibody-Ligand Binding Kinetics on the Pharmacokinetics of High-Clearance Ligands" AAPS Annual Meeting, AAPS (2008)
"Investigating the Contribution of the Neonatal Fc Receptor at the Blood Brain Barrier" AAPS Annual Meeting, AAPS (2007)
"PKPD of Antibodies" American College of Clinical Pharmacology, Annual Meeting, AACP (2007)
"PBPK Analysis of the Effects of IVIG and FcRn on IgG Tissue Disposition" National Biotechnology Conference, AAPS (2007)
"Utility of PKPD modeling in the comparability assessment of therapeutic proteins - An academic perspective" National Biotechnology Conference, AAPS (2007)
"Where did my Mab go?" National Biotechnology Conference, AAPS (2007)
"Monoclonal antibody pharmacokinetics" Symposium of the future of monoclonal antibody biotherapeutics: Production and Development, New York Academy of Sciences (2007)
