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A front-page story in the New York Times details the progress of a Perelman School of Medicine team in using genetically engineered versions of leukemia patients' own T cells to fight their cancer; an approach which has now been used in 12 patients, 9 of whom responded to the therapy -- including two children.

"Our goal is to have a cure, but we can't say that word," said the study's leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center.

He hopes the new treatment will eventually replace bone-marrow transplantation, an even more arduous, risky and expensive procedure that is now the last hope when other treatments fail in leukemia and related diseases.

Researchers at Penn’s Abramson Cancer Center recently published study results considered to be a major breakthrough in cancer treatment for chronic lymphocytic leukemia. The study, published in The New England Journal of Medicine, used patients’ own T cells genetically engineered to kill cancer tumors, and has been hailed as a cancer breakthrough 20 years in the making.

“What we’re doing falls under the area of personalized medicine in the extreme sense – using a person’s own white blood cells or tumor cells to develop a personalized vaccine,” said Carl H. June, MD, director of translational research at the Abramson Cancer Center (ACC), who is overseeing the development of these vaccines.

Dr. June, widely regarded as one of the world’s leading cancer immunologists, has spent years conducting research at the ACC with modified T-cells, cells in the body that are capable of recognizing, attacking, and destroying foreign invaders, and assembling a team of physician-scientists to advance immunotherapy for many types of cancer.

Immunotherapy removes cells from patients and modifies them in Penn’s Clinical Cell and Vaccine Production Facility (CCVPF), a Abramson Cancer Center Core Facility under the direction of Bruce L. Levine, PhD. The modified cells are infused back into the patients following chemotherapy.

“This isn’t a drug in a bottle or a vaccine in a vial,” Dr. June said. “This is more like a next-generation blood transfusion.”

The recent immunotherapy discovery in chronic lymphocytic leukemia is an exciting turning point in the way cancer is treated and will provide hope to thousands of cancer patients and their families, according to Dr. June.

Here are a few examples of leading-edge treatments for cancer being developed right here at Penn Medicine.

Immunotherapy for Lymphoma

Stephen J. Schuster, MD
Director, Lymphoma Translational Research Center
Lymphomas can be a complex and difficult-to-treat cancers and treatments are often toxic to normal organs and not entirely effective. However, Dr. Schuster and researchers at the Abramson Cancer Center may have found a way of improving the therapy available in the treatment of lymphoma and related diseases. A clinical trial using expansion technology to test infusions of T-cells, following chemotherapy for chronic lymphocytic leukemia is showing promising results. In another study, personalized vaccines made with patients own tumor cells, were found to significantly improve the average remission period for patients with the disease.

Immunotherapy for Mesothelioma and Pleural Malignancies

Steven M. Albelda, MD
Vice Chief, Pulmonary, Allergy, and Critical Care Division
A current phase I/II trial investigates the effectiveness of gene therapy when used in combination with chemotherapy for the treatment of mesothelioma. There is evidence that this method of treatment will prove quite effective, and the hope is that it may someday be integrated into the standard of care for mesothelioma patients. This trial is specific to mesothelioma, but Dr. Albelda and his team are hopeful that this therapy will show practical applications for other cancers of the pleural cavity.

Immunotherapy for Pancreatic Cancer

Robert H. Vonderheide, MD, DPhil
Associate Director for Translational Research
An early-stage clinical trial may lead to new treatment options for patients with advanced pancreatic cancer. The treatment appears to work differently than expected, attacking tumors primarily by altering their surrounding tissue. This means that attacking the dense tissues surrounding the cancer is another approach to consider. Similar to attacking a brick wall by dissolving the mortar in the wall, the immune system is able to eat away at this tissue surrounding the cancer, and the tumors fall apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer.

Immunotherapy for Ovarian Cancer

George Coukos, MD, PhD
Director, Penn’s Ovarian Cancer Research Center
The treatment for ovarian cancer usually involves a combination of surgery and chemotherapy, but for the majority of women with the disease the standard treatment stops working. New approaches to treating ovarian cancer are necessary to improve survival rates and immunotherapy is proving to be hopeful for patients. At the time of surgery, the patient’s tumor is saved for future use in a vaccine. After completing standard chemotherapy, patients will then have access to individualized immunotherapy treatments using their own tumor tissue to fight their cancer should it recur. Dr. Coukos is leading a number of phase I and II clinical trials testing the effectiveness of these vaccines and is seeing promising results. In addition, Dr Coukos and his colleagues at the Ovarian Cancer Research Center are launching T cell based immunotherapies using blood-derived, engineered T cells, or tumor-derived T cells.

Immunotherapy for Prostate Cancer

Jihyun Lee
Post Doctoral Researcher in Dr. June’s lab
While hormone therapy has worked to delay the progression of cancer, it is not curative and in some advanced malignant forms of prostate cancer, the cancer will progress. Dr. Lee’s research focuses on the development and optimization of an anti-PSMA CAR that would be used in adoptive T cell clinical trials to treat malignant and recurring prostate cancers.

Dr. Lee is optimistic that it is now possible to develop and deliver a sufficient number of properly activated T cells that have sufficient power to overcome tolerance and eradicate prostate cancer. A clinical trial will soon be in place, which would determine the effectiveness in patients.

Immunotherapy for Breast Cancer

Brian Czerniecki, MD, PhD
Co-Director, Rena Rowan Breast Center
Surgical Director, Immunotherapy Program
A phase II clinical trial sheds new light on how vaccines can inhibit tumor growth, lessen the severity of the disease, and prevent its recurrence in patients with early stage breast cancer, ductal carcinoma in-situ (DCIS). Over-expression of the HER-2/neu gene is linked to about 50 to 60 percent of DCIS cases, and helps predict the severity of the disease, as well as the risk of recurrence of invasive breast cancer. By treating dendritic cells, specialized white blood cells that play a major role in activating immune response, with HER-2/neu, Dr. Czerniecki produced a vaccine that may prompt an immune response. Results have shown that nearly all patients exhibited an initial immune reaction to the vaccine, and half showed markedly reduced levels of HER-2/neu expression, leading to overall improvement in the severity of the disease.

Immunotherapy for Chronic Lymphocytic Leukemia

David L. Porter, MD
Director, Blood and Bone Marrow Transplantation Program
The latest ground-breaking clinical trial among advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells showed extreme promise demonstrating sustained remissions of up to a year. The findings are the first demonstration of the use of immunotherapy to create “serial killer” T cells aimed at cancerous tumors, providing a tumor-attack roadmap for the treatment of other cancers.

“The therapy could replace the need for bone marrow transplantation. This is currently the only curative therapy for most patients with leukemia” says Dr. Porter.

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the third of four posts about the latest findings in treating breast cancer.

BMI and Cancer Outcomes
In recent years, the belief that obese breast cancer patients have worse outcomes has become somewhat entrenched in the cancer community. A North American Breast Cancer Group study presented in 2010 appeared to be confirmed those findings. But just one year later, data presented at ASCO 2011 data (abstracts 513, 514, 515), appears to contradict that belief.

Angela DeMichele, MD, associate professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, said the combined analysis of five National Cancer Institute studies demonstrate no compelling evidence that obesity, a body mass index (BMI) of 30 or more, compromises breast cancer survival. The studies also show BMI does not affect estrone (the estrogen left after menopause, made primarily by body fat) levels in postmenopausal women.

Despite the discrepancy in the findings, Dr. DeMichele reinforced the need to encourage obese women to lose weight and provide active support to women undergoing hormonal treatment to help them avoid weight gain.

Exemestane Yields Impressive Results in Prevention Study
One of the most noted studies at this year's ASCO meeting was the MAP3 trial (abstract 504), which presented persuasive evidence that the aromatase inhibitor exemestane, has a significant effect in preventing invasive breast cancer in medium to high risk postmenopausal women. The study, released simultaneously in the New England Journal of Medicine, represents a "huge victory for chemoprevention," in the words of the Angela Bradbury, MD, who presented the study at the ASCO meeting.

In this large, multinational study, women who received exemestane had a 65 percent reduction in invasive breast cancer. This is a superior result to the 50 percent reduction seen in studies utilizing tamoxifen and raloxifen.

Over a three-year period, exemestane reduced the incidence of ductal carcinoma in situ and other precancerous conditions, and appeared to reduce the incidence of more aggressive breast cancers in those women who did develop the disease. In addition, the study found that the side effects; hot flashes, insomnia, and arthralgia; were not excessive and generally well tolerated by the study participants. Serious toxicities including fractures, other cancer, osteoporosis and cardiovascular events were not seen in the study participants.

While the MAP3 results are without question important and exciting, some experts question whether healthy women will take a drug that is associated with a spectrum of menopausal type symptoms, even to achieve an important goal of reducing invasive breast cancer. The answer may depend on a variety of factors including:

• Level of individual risk
• Age
• Overall health
• Conversations between women and their doctors as they become aware of this new study and its implications for preventing the second leading cause of cancer deaths in women

Abstracts can be found on the 2011 ASCO meeting website.

Learn more about breast cancer treatment at Penn’s Abramson Cancer Center.

Are you at risk for breast cancer? Attend Penn Women’s Cancer Conference – Focus on Your Risk of Breast/Ovarian Cancer

Are you a breast cancer survivor? Attend the Penn Women’s Cancer Conference – Life after Breast Cancer

Coming up next, The Value of Adjuvant and Neoadjuvant Therapy.

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the second of four posts about the latest findings in treating breast cancer. 

One of the larger trends in cancer treatment, especially breast cancer treatment, is the increasing ability to identify biologic subtypes of the disease and the need for better prognostic biomarkers, or biomarkers that provide information regarding outcome without regard for therapy.

Angela DeMichele, MD, MSCE

At the 2011 ASCO conference, Angela DiMichele, MD, MSCE, assistant professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, talked about the important role biology plays in identifying these markers. As co-program leader of the Abramson Cancer Center's National Cancer Institute (NCI)-approved breast cancer program, she discussed one such marker, Ki-67, and intrinsic genetic subtypes.

Two studies (Abstracts 500 and 501) provide support for the validity of Ki-67 as a means of identifying highly proliferative tumors and those that are more likely to respond to specific chemotherapy regimens. Ki-67 is a cancer antigen that is found in growing, dividing cells but is absent in the resting phase of cell growth. This characteristic makes Ki-67 a good tumor marker. This test is done on a sample of tumor tissue, to help predict your prognosis.

Many studies have been done to determine Ki-67's value as a tumor marker test. Researchers agree that high levels of Ki-67 indicate an aggressive tumor and predict a poor prognosis and tumors that tested positive with high levels of Ki-67, have a higher risk of recurrence.

Perhaps more intriguing is the emergence of intrinsic subtypes of breast cancer. Gene expression studies have identified several distinct breast cancer subtypes. The value of this information is less clear, but understanding the specific biologic characteristics that influence these subtypes may help determine which patients will respond to which therapies.

Cancer researchers now understand that breast cancer is a spectrum of diseases, ranging from those that are more endocrine driven to those that are more chemosensitive. These findings reinforce the need for accurate molecular profiling for all breast cancer patients.

OncotypeDX has become a standard means for molecular profiling and guiding breast cancer treatment decisions, but another, potentially even more comprehensive tool is on the horizon. PAM-50 screens for 50 genes and is potentially more sensitive, but is not yet clinically available. Further studies are needed to validate its use.

Abstracts can be found on the 2011 ASCO meeting website.

Learn more about breast cancer treatment at Penn’s Abramson Cancer Center.

Are you at risk for breast cancer? Attend Penn Women’s Cancer Conference – Focus on Your Risk of Breast/Ovarian Cancer

Are you a breast cancer survivor? Attend the Penn Women’s Cancer Conference – Life after Breast Cancer

Coming up next, How Weight and Hormones Affect Breast Cancer Outcomes.

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the first of four posts about the latest findings in treating breast cancer.

The summary of the latest news in breast cancer treatment was delivered in rapid-fire style at the Abramson Cancer Center’s 2011 Update in Breast Cancer ASCO summary course. Unfortunately, many of those attending the annual conference thought the news was "not as exciting as last year," because of the lack of any single, major breakthrough.

At the 2010 conference, Penn cancer researchers highlighted the promising results of targeted immunotherapy in treating metastatic breast cancer.

While there may have been no single big story, significant data were presented across the full platform of breast cancer-related topics: from prevention to neoadjuvant therapy and managing metastatic disease. Major emphasis was placed on improved understanding of the biology of breast cancer and the development of more targeted therapies tailored to match the specific genetic profiles of patients.

From the Headlines: FDA Approval for Bevacizumab

David M. Mintzer, MD

One issue that has been in the headlines during the past months is the status of FDA approval of bevacizumab (Avastin®) for first-line of treatment of HER2-negative metastatic breast cancer in combination with paclitaxel.  Bevacuzumab received fast track approval in 2008. Subsequent studies, including those presented at ASCO 2011, demonstrated modest improvements in progression-free survival, but none in overall survival or improvement in disease-related symptoms.  The down sides of the drug are its toxicity and high costs of administration.

Just hours after the update concluded, the Oncologic Drugs Advisory Committee voted 6-0 to withdraw FDA approval for bevacizumab for treating HER2-negative metastatic breast cancer. While the committee vote was unanimous, the hearing itself was marked by emotional pleas from breast cancer patients who believe they are benefitting from bevacizumab treatment.   The recommendation is not binding and a final decision is expected in September. It also does not affect insurance coverage or availability at this time, or the drug's approval for other cancer types.

"We know this drug has activity in some women," said David Mintzer, MD, clinical associate professor and chief of hematology/oncology, Pennsylvania Hospital. "We have all seen it and we know that activity stops when you stop giving the drug, but we just know now how to predict which women will get that benefit."

Abstracts can be found on the 2011 ASCO meeting website.

Learn more about breast cancer treatment at Penn’s Abramson Cancer Center.

Are you at risk for breast cancer? Attend Penn Women’s Cancer Conference – Focus on Your Risk of Breast/Ovarian Cancer

Are you a breast cancer survivor? Attend the Penn Women’s Cancer Conference – Life after Breast Cancer 

Coming up next, Understanding the Biology of Breast Cancer.