© 2008 Dana-Farber Cancer Institute. All Rights Reserved. No part of this report may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by an information storage or retrieval system, without permission in writing from Dana-Farber Cancer Institute. For additional information, please contact Kathleen Hughes at (617) 582-8343. Dana-Farber Cancer Institute | September 2008 The de Beaumont Fellow: Karen Anderson, MD, PhD THE DE BEAUMONT FOUNDATIONHarnessing the Power of the Immune System to Fight Cancer 1 The human immune system holds great promise as a powerful weapon against cancer. Dana-Farber’s Cancer Vaccine Center (CVC) strives to tap into that enormous potential by developing tools and methods for manipulating key components of the immune system to attack tumors. CVC de Beaumont Fellow Karen Anderson, MD, PhD, has focused specifically on developing and testing immunotherapies for breast cancer patients. Her outstanding work exemplifies the kind of research the CVC was designed to cultivate. Dr. Anderson has spent the past year continuing to lead a clinical trial of an exciting new breast cancer vaccine (see figure below). Meanwhile, she and her collaborators have also validated and exploited a novel technology for identifying factors that may play a pivotal role in successful anti-tumor immune responses. These factors could one day serve as tools for detecting breast cancers earlier, for gauging the effectiveness of a given therapy in individual patients, and for recognizing early signs of disease progression. They could also help pave the way to designing better breast cancer vaccines in the future. The de Beaumont Fellowship has given Karen Anderson, MD, PhD, crucial support over the past three years. To make the breast cancer vaccines used in Dr. Anderson’s clinical trial, researchers first remove tumor cells from a breast cancer patient and take them to the CVC’s Connell and O’Reilly Families Cell Manipulation Core Facility. There, medical technologists infect the cells with viruses that contain the gene encoding GM-CSF—a protein that stimulates certain components of the patient’s immune system to respond to the vaccine. The cells are then irradiated before being injected back into the same patient. This step causes the cells to die shortly afterward, giving the vaccine a brief window of time to jump-start an anti-tumor immune response while ensuring that the modified tumor cells in the vaccine cannot themselves give rise to tumors within patients. Using vaccines to combat breast cancerBiomarkers: Detecting and Monitoring Tumors 2 Even before a tumor becomes visible on a mammogram, its precursors quietly sow the seeds of malignancy. To root out the disease before it takes hold, doctors need a sensitive, reliable, non-invasive method for detecting these potential killers—ideally, an inexpensive blood test. The key to developing such an assay lies in identifying biological indicators of disease called biomarkers. These molecules, produced either by the tumor itself or by the body in response to the tumor, could alert doctors to the presence of malignant cells long before the cancer would be detectable by conventional means. This, in turn, could lead to earlier treatment and better prognoses for patients. Biomarkers could be useful not only for telling whether a patient has a breast tumor but what kind of tumor it is. Some tumors are far more aggressive than others, and it isn’t easy to tell which ones will respond more readily to treatment. If researchers could identify a biomarker in the blood that correlates with more lethal tumors, they could use that as a tool for deciding which patients need more aggressive therapy and which ones call for a less radical approach. Biomarkers can also be used to monitor the effectiveness of a therapy. For example, if a specific biomarker associated with a tumor begins to disappear from a patient’s blood over the course of treatment, doctors might conclude that patient is responding to the therapy. If the biomarker levels stay the same or begin to rise, that might indicate the therapy isn’t working, and the physician might opt to try a different treatment instead. Also, after a patient has completed therapy, doctors might monitor her blood for the same biomarker, whose presence could indicate disease recurrence. Potential uses for breast cancer biomarkers Before treatment During treatment After treatment Early detection & diagnosis of tumors Monitoring effectiveness of therapy Guidance in weighing treatment options Looking for signs of disease progression Detecting disease recurrence Dr. Anderson is identifying biomarkers in the blood of breast cancer patients that could one day be used as part of a non-invasive test for detecting and monitoring breast tumors.Autoantibodies: Biomarkers in the Blood 3 Much of Dr. Anderson’s research has focused on autoantibodies—a particular type of immune biomarker that circulates freely in the bloodstream. Naturally produced by cancer patients’ immune cells in response to tumor antigens, autoantibodies may contain valuable information about the tumor itself as well as the immune system’s response to that tumor. But to access this precious knowledge, scientists must first find ways to rapidly identify autoantibodies from patient blood samples, focusing on those that hold the greatest promise as biomarkers. In a study published earlier this year, Dr. Anderson used an exciting new technology to do just that. She and her collaborators at the Harvard Institute of Proteomics used a new kind of protein microarray (see figure below) that allowed them to simultaneously detect antibodies to antigens derived from 1116 cancer-related genes, 539 of which had been previously linked to breast cancer. Probing the array with blood-derived samples from cancer patients, she and her colleagues detected antibodies to the tumor suppressor protein p53 in samples from breast and ovarian cancer patients. The researchers also found