Ovarian, Uterine, and Cervical Cancers

Current Projects
Christopher A. Klebanoff, MD

A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. Thus far, this promising form of cancer immunotherapy has failed to work in most patients with cancers arising from solid organs, the leading cause of cancer-related deaths in adults. Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. Dr. Klebanoff seeks to use a genetic engineering approach to simultaneously address both these issues. Success of these efforts would be a decisive step forward toward extending the ability of ACT to deliver potentially curative responses in patients with common cancers, including those arising from the breast, uterus, cervix and colon.

Project title: "Clinical development of next-generation T cell receptor (TCR)-based adoptive immunotherapies for the treatment of patients with common epithelial malignancies"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Michel Sadelain, MD, PhD, and Larry Norton, MD
Cancer Type: Gynecological, Kidney and Bladder, Breast
Research Area: Immunotherapy
Kathrin Leppek, PhD

Dr. Leppek [Layton Family Fellow] aims to combine RNA and ribosome biology with developmental biology to investigate how cells regulate protein synthesis through a process called translation. This process requires regulatory mechanisms to fine-tune when and where genes are expressed. Defective expression of certain genes gives rise to uncontrolled growth and metastasis of cancer cells. She will identify and characterize molecular components that play a functional role in mediating translational control during embryogenesis. This will be invaluable for our understanding of how deregulation of accurate gene expression underlies human diseases such as cancer.

Project title: "Mechanistic characterization of 5’UTR RNA elements that confer translational specificity to shape vertebrate embryonic development"
Institution: Stanford University
Named Award: Layton Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Maria Barna, PhD
Cancer Type: Blood, Gastric, Gynecological, Breast, Colorectal, Lung, Pancreatic
Research Area: Developmental Biology
Jason M. Sheltzer, PhD

Dr. Sheltzer studies how aneuploidy, or having too many or too few chromosomes in the cell, affects cancer development and treatment. Approximately 55% of breast cancers have an extra copy of one part (called the “q arm”) of chromosome 1. His lab is developing cutting-edge chromosome engineering technology to eliminate the extra copies of 1q from breast cancer cell lines and determine whether this prevents the cells from forming tumors. Additionally, they will test whether aneuploidy causes ovarian cancer cells to be sensitive to any chemotherapies, with the goal of identifying a drug that specifically kills cells with extra copies of chromosome 1q without affecting normal cells. These experiments could lead to highly effective “chromosome-specific” therapies based on aneuploidy.

Project title: “Are cancers addicted to aneuploidy?”
Institution: Cold Spring Harbor Laboratory
Award Program: Innovator
Cancer Type: Gynecological, Colorectal, Sarcoma, All Cancers
Research Area: Chromosome and Telomere Biology
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