John G. Frelinger, Ph.D.

John G. Frelinger, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 704
Rochester, NY 14642

Research Bio

My laboratory has a number of interests united by the common theme of T cell recognition. One focus of research has been the generation and maintenance of effective T cell responses to tumors. It has become apparent that anti-tumor responses can be directed against differentiation antigens. Thus, even with multiple mechanisms of establishing and maintaining tolerance, tolerance is not absolute. We hypothesize that it is possible to direct an effective response against tumors by inducing an autoimmune response to organ-specific antigens. To examine this hypothesis, we will use transgenic mice lines we have developed which specifically express human PSA in the prostate and investigate how this expression affects their ability to generate CTL responses to human PSA using novel immunization strategies.

In this light, we have been working on developing novel viral vectors for immunization. Helper free herpes amplicons, plasmid based vectors that have an extremely large coding capacity, are attractive viral vaccine candidates for expressing recombinant proteins in vivo for immunization. The amplicon system has particular promise since it encodes no viral gene products and we have shown it very effectively infects dendritic cells. In collaboration with Edith Lord and in conjunction with Tom Foster's laboratory in the Department of Imaging Sciences, we have devised imaging approaches to look at the early steps in immunization and at the effector T cells generated. These studies will contribute to the rational design of immunotherapy for tumors as well as for HIV. We also believe that many of the techniques and approaches will be applicable to other infectious agents as well. In this regard, we are collaborating with investigators at University of North Carolina to identify T cell epitopes of Francisella tularensis. Francisella tularensis (FT) is a gram negative bacterium that is able to infect a wide range of mammalian hosts. FT has several properties that suggest could be developed as a biological weapon, including its ability to be aerosolized and its low LD50. Indeed, it has been asserted that FT was used as a bioweapon in World War II. Unfortunately relatively little information is available concerning the detailed cellular mechanism of resistance to re-infection either in humans or in experimental animals. However, as expected for a pathogen that grows largely intracellularly, T cells are believed to be a critical component in resistance to reinfection and recovery from primary infection. My laboratory has developed a technique called the TCAD ( the T-Cell antigen discovery technique) to identify and improve T cell epitopes, originally in the context of tumor vaccines. We have recently modified this system to large-scale screens for the identification of T cell epitopes from FT using this system which takes advantage of the tremendously enhanced efficiency particulate antigen cross-priming and a novel reporter system of T cell activation. It is hoped that the identification of the T cell epitopes recognized will yield to a batter understanding of the nature of a protective response and ultimately a defined vaccine.

Patents

Transgenic Mice Expressing Human PSA

United States Serial NO.: 08/797,722
Filed Date: February 11, 1997
Title: Prostate Specific Regulatory Nucleic Acid Sequences and Transgenic Non-Human Animals Expressing Prostate Specific Antigen
Invented by: John Frelinger, Richard Barth, Chungwen Wei
Transgenic Mice Expressing Human PSA

United States Serial NO.: 09/607,549
Filed Date: June 7, 2001
Title: Prostate-Specific Regulatory Nucleic Acid Sequences and Transgenic Non-Human Animals Expressing Prostate Specific Antigen
Invented by: John Frelinger, Richard Barth, Chungwen Wei
Human Glandular Kallikrein (hK2)-Specific Monoclonal Antibodies that Enhance or Inhibit the Enzymatic Activity of hK2

United States Serial NO.: 10/491,761
Filed Date: October 3, 2002
Title: Human Glandular Kallikrein (HK2)-Specific Monoclonal Antibodies that Enhance or Inhibit the Enzymatic Activity of HK2
Invented by: John Frelinger, Terrence Fisher, Mary Ann Nocera-March, Edith Lord
Protease Activated Cytokines to Enhance Immune Reponses to Tumors

United States Serial NO.: 13/639,006
Filed Date: March 31, 2011
Title: Protease Activated Cytokines
Invented by: John Frelinger, John Puskas, Baek Kim, Mark Sullivan

Awards & Honors (National)

Junior Faculty Research Award | American Cancer Society 1986 - 1988
Jane Coffin Childs Fellowship 1981 - 1983
National Merit Scholarship 1971 - 1975

Awards & Honors (Local)

Alumni Gold Medal Teaching Award 2012
AAI Education Committee | American Association of Immunologists 2011 - 2014
Special Commendation Teaching-Medical School 2002
Faculty Speaker, Medical School Class of 2000 Awards Ceremony 2000
Distinguished Speaker | University of Texas at San Antonio 2000
Herbert W. Mapstone Prize for Teaching Excellence 1998
Special Commendation Teaching-Medical School 1996
Herbert W. Mapstone Prize for Teaching Excellence 1995
Special Commendation Teaching-Medical School 1994
Andrew W. Mellon Deans Teaching Scholar | Excellence in Teaching and Research 1991 - 1993
American Cancer Society Senior Fellowship, California Division 1983 - 1984
B.S. with Distinction and Departmental Honors 1975
2014 Chair Education Committee (AAI) | AAI

Recent Journal Articles

Showing the 5 most recent journal articles. 85 available »

2013 Jun
Gerber SA, Sedlacek AL, Cron KR, Murphy SP, Frelinger JG, Lord EM. "IFN-? mediates the antitumor effects of radiation therapy in a murine colon tumor." The American journal of pathology.. 2013 Jun; 182(6):2345-54. Epub 2013 Apr 12.
2013 Mar
Gerber SA, Sorensen EW, Sedlacek AL, Lim JY, Skrombolas D, Frelinger JG, Lord EM. "Local expression of interleukin-2 by B16 melanoma cells results in decreased tumour growth and long-term tumour dormancy." Immunology. 2013 Mar; 138(3):280-92.
2011 Jun
Puskas J, Skrombolas D, Sedlacek A, Lord E, Sullivan M, Frelinger J. "Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases." Immunology. 2011 Jun; 133(2):206-20. Epub 2011 Mar 23.
2011 Mar
Valentino MD, Maben ZJ, Hensley LL, Woolard MD, Kawula TH, Frelinger JA, Frelinger JG. "Identification of T-cell epitopes in Francisella tularensis using an ordered protein array of serological targets." Immunology. 2011 Mar; 132(3):348-60. Epub 2011 Jan 07.
2011
Valentino M.D.; Abdul-Alim C.S.; Maben Z.J.; Skrombolas D., Hensley L.L.; Kawula T.H.; Dziejman M.; Lord E.M.; Frelinger J.A.; Frelinger J.G. "A broadly applicable approach to T cell epitope identification: Application to improving tumor associated epitopes and identifying epitopes in complex pathogens". Journal of Immunological Methods (in press). 2011; . Link

Current Appointments

Professor - Department of Microbiology and Immunology (SMD) - Primary

Education

PhD | Biochemistry | California Institute of Technology1980
BS with Distinction and Departmental Honors | Biology | Stanford University1975

Post-Doctoral Training & Residency

Senior Postdoctoral Fellow, American Cancer Society, California Division, Stanford University. Mentor: Dr. C.G. Fathman, Immunology 1984
Jane Coffin Childs Fellow, Immunology, Stanford University, Mentor: Dr. C.G. Fathman, Immunology 1983
NIH Postdoctoral Fellow, Caltech, Pasadena, CA. Mentor: Dr. Leroy Hood, Molecular Biology 1981