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Wednesday, February 1, 2012

Immunotherapy - a Personalized Approach to Medicine

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.

3 comments:

  1. can you please, please, please, please begin immunotherapy trials for sarcoma? please.........

    ReplyDelete
    Replies
    1. Thank you so much for your interest in immunotherapy clinical trials at Penn.

      The NYESO TCR sarcoma protocol is enrolling patients aged 4 to 35 year old.

      For more information, contact a research coordinators:

      Margie Tartaglione, RN Research Coordinator (Lead), BMT Quality Coordinator
      PHONE: (215) 590-4029
      EMAIL: TARTAGLIONE@email.chop.edu

      Christine Strait Research Coordinator (Lead)
      PHONE: (215) 267-425-5837
      EMAIL: straitc@email.chop.edu

      Delete
  2. This comment has been removed by the author.

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