2005 Recipient Jose Conejo-Garcia, MD, PhD

Jose Conejo-Garcia, MD, PhD

Vascular Leukocytes as novel anti-tumor therapeutic targets

Project Summary

The current therapies against cancer show significant limitations. Alternative therapies are therefore needed. Since tumors cannot grow in the absence of vascular support, tumor blood vessels represent important therapeutic targets. We have identified a novel population of tumor-infiltrating leukocytes, termed Vascular Leukocytes (VLCs), which have the capacity to form blood vessels in the ovarian cancer microenvironment. Temporary elimination of VLCs in mouse models does not harm the animal and results in a dramatic decrease in tumor growth, due to the specific disruption of tumor vasculature. These experiments are highly relevant for future human treatments, since VLCs are also strongly represented in human ovarian cancer.

In order to design clinically effective ways of impeding tumor vascularization, we are investigating the precise contribution of VLCs to vascularization at different stages of tumor progression. Interestingly, VLCs originate from leukocytes that have the potential to orchestrate an anti-tumor immune response. We are therefore determining the mechanisms whereby ovarian cancer regulates the transformation of latent immuno-stimulatory cells (VLC precursors) into immunosuppressive endothelial-like cells (VLCs), which act as accomplices in tumor growth and dissemination. Since VLCs exhibit a distinct profile of markers, we are also testing new immunotherapies to target determinants that are specific to VLCs and are absent in normal adult blood vessels. Our long-term goal is to reverse the angiogenic capacity of VLCs while exposing their potential as active immunogenic, anti-tumor antigen-presenting cells. The identification of VLCs as significant contributors to tumor vascular support will prove to be highly beneficial to the treatment of human ovarian cancer.

Areas of Research:

Bio

Dr. Conejo-Garcia is an Associate Professor in the Immunology Program at the Wistar Institute in Philadelphia. Prior to moving to Wistar, he was an Assistant Professor of the Departments of Microbiology and Immunology, and of Medicine at Dartmouth Medical School, as well as member of the Immunobiology Program at the Norris Cotton Cancer Center.

Dr. Conejo-Garcia is known for his research in the immunobiology of ovarian cancer, a field in which he has published >20 papers in top-ranked journals. His primary areas of interest are in the development of novel treatments that boost spontaneous anti-tumor immune responses against ovarian cancer and make them therapeutically relevant. To overcome the mechanisms of immunosuppression orchestrated by the tumor microenvironment, Dr. Conejo-Garcia has developed novel host conditioning strategies based on the use of nanoparticles, immunotoxins and T cell adoptive therapies. He is the recipient of the 2006 Liz Tilberis Award for Excellence in Ovarian Cancer Research from the Ovarian Cancer Research Fund (OCRF) and is the Principal Investigator of an NCI R01 award to define the role of inflammatory cells in ovarian cancer and another pending NCI R21 grant to re-program immune cells at tumor locations with nanoparticles.

Before joining Dartmouth in September of 2005, Dr. Conejo-Garcia spent more than four years at the University of Pennsylvania working in Dr. Coukos group at the Center for Research in Reproduction and Women’s Health on the immunobiology of ovarian cancer.

Dr. Conejo-Garcia received his medical degree from the University of Zaragoza (Spain) in 1990. While completing a residency in Clinical Chemistry at the University Hospital of Guadalajara (Spain), he received a fellowship from the Spanish government to start a Ph.D. in Molecular Oncology at the University of Alcala (Spain). Dr. Conejo-Garcia received his title of board certified specialist in Clinical Chemistry (European Union) in 1996 and finished his Ph.D (Cum Laude unanimously) in 1998. He then received a different post-residency fellowship from the Spanish government for a postdoctoral stay at the University of Bern (Switzerland), where he spent one year working on pancreatic cancer. Before moving to the US, he spent two additional years working on the identification of novel peptides with immunological and antimicrobial activity at IPF Pharmaceuticals (Hanover, Germany), where he discovered and patented most human beta-defensins. Dr. Conejo-Garcia has published 42 scientific articles and 4 book chapters, and is co-author of 3 patent applications from different institutions.

In addition to the Liz Tilberis honor and his 2 post-residency fellowships from the Spanish government, Dr. Conejo-Garcia has received several awards, including the 2004 basic science poster award at the 35th Annual Meeting of Society of Gynecologic Oncologists, an ovarian spore developmental pilot project award by the Fox Chase Cancer Center Specialized Program of Research Excellence (SPORE) in Ovarian Cancer in 2005 and the 2003 Health investigation award of the University Hospital of Guadalajara (Spain).

Watch an interview with Dr. Conejo-Garcia on the Dartmouth website