After living with chronic lymphocytic leukemia (CLL) for 14 years, James Smith (not his real name) faced a pivotal decision. Chemotherapy was no longer sufficient to keep his disease in remission; he had to choose between two next-stage treatment options.

One, a bone marrow transplant, had a 10 to 20 percent chance of life-threatening complications, a 50 percent chance of long-term remission, and required anti-rejection drugs for the rest of his life.

The other was to participate in the pilot phase of a clinical trial using autologous cellular immunotherapy run by David L. Porter, MD, director of Blood and Marrow Transplantation.

Smith opted for number two.

As a scientist, “I understood the clinical protocols, the risks and the side effects. It was one of those things that should work based on the science, which looked solid,” said Smith, a married father of four adult children. But, he added, “that’s never a given when you’re talking about a biological system.”

Personalized Vaccines Show Promise

“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."- Carl H. June, MD

Drawing upon decades of research and clinical trials in DNA modification techniques and immunology, Penn researchers are refining a new form of personalized therapeutic vaccines called autologous cellular immunotherapy. “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, who is overseeing the development of these vaccines.

Unlike traditional vaccines that protect against future exposures to a pathogen, personalized immunizations treat an existing disease or infection. Phase 1 and 2 clinical trials currently underway at Penn are using this type of immunotherapy for blood cancers such as chronic lymphocytic leukemia, solid tumors such as ovarian and breast cancer, and viruses such as HIV.

These vaccines stand to provide hope to thousands of cancer patients. Another trial underway, run by oncologic surgeon Brian Czerniecki, MD, PhD, is testing a personalized vaccine for patients with ductal carcinoma in situ, which accounts for as many as 25 percent of the 260,000 new breast cancer cases each year.

Until recently, therapeutic immunization occurred in one rare place in medicine: after exposure to rabies. Now, these newer vaccines are showing promise. “This isn’t a drug in a bottle or a vaccine in a vial,” June said. “This is more like a next-generation blood transfusion.”

In Smith’s clinical trial protocol, “blood came out of one arm and went into a centrifuge,” he said. “They separated out the white blood cells and returned the rest into my other arm. All they took was half a cup.” Next, his T cells were genetically modified at Penn’s Clinical Cell and Vaccine Production Facility (CCVPF) so they would kill mature B lymphocytes, including his cancer cells.  The CCVPF plays a key role in this research, providing regulatory and scientific support to clinicians. Bruce L. Levine, PhD, Facility director, worked with June to refine and advance the therapeutic vaccine used in the CLL protocol.

Two weeks after his infusion, Smith woke up with what felt like the flu. He said, “Great, the war has started.“ That was the indicator everyone was looking for.

In September, over the course of three closely monitored days, Smith was infused with those modified cells and had no reaction to the infusion. Two weeks after the infusion he woke up with what felt like the flu. “I said ‘Great, the war has started,’” he recalled. “That was the indicator we were all looking for -– when my genetically modified T cells started killing off the CLL cells.”  The reaction against the patient’s CLL was so strong he required hospitalization to manage side effects and for monitoring. But, Smith said, after four days in the hospital, he was released and has since felt “terrific.” 

Smith’s hope was that the pilot phase clinical trial treatment would help him defer bone marrow transplantation as long as possible. To his surprise, the treatment appears to have completely cleared his body of CLL “Right now they can’t find any disease in my bone marrow and blood and it has been six weeks since my treatment,” said Smith, overcome with emotion.

Hope for the Future

The journey toward future widespread use of personalized therapeutics is arduous;  it requires a lengthy FDA approval process, the challenge of validating and advancing the science, and the need to raise anywhere from $5 to $50 million. “It’s like running two or three marathons one after another!” said Pablo Tebas, MD, principal investigator of the AIDS Clinical Trials Unit.

And, so far, the amount of available funding lags behind the science of personalized therapeutics, given the state of the economy, NIH funding levels, and the fact that the individualized approach is so different from factory-produced vaccines or pills

If effective, “this kind of treatment might be developed for patients with all different sorts of cancers. It is really the beginning of the very new field of immune therapy.”- David L. Porter, MD

Still, researchers are optimistic. Porter said that it’s unclear if Smith’s pilot treatment will lead to long-term remission, a low level of the disease, or a cure. However, “two of the three CLL patients who have so far participated in this clinical trial -- and were resistant to all other therapies -- appear to be in complete remission after this cell therapy. And the third patient had an excellent though partial response,” Porter said. “It’s very early in the trial, but our initial experience has been very exciting You don’t see completely new therapies work so effectively very often.”

The field of personalized vaccines is at least a decade away from widespread clinical use, but early signs are promising. Referring to the responses of the CLL patients, Porter said that, if effective, “this kind of treatment might be developed for patients with all different sorts of cancers. It is really the beginning of the very new field of immune therapy.”

Slideshow: The Basic Steps to Produce a Vaccine

  1. Washing Cells: Cells collected for vaccine preparation are washed with cell processing solution to remove any residual blood components that may interfere with the vaccine manufacturing process. This automated washing device separates out the cells into collection bags for further cell processing.
  2. Separating Desired Cell Groups: Depending on the type of vaccine being produced, it may be necessary to only grow up certain cell types but not others.  This instrument separates out the desired cell groups, based on size and density.  The end product is a pure group of the these cell types.
  3. Manufacturing Vaccine: The cell vaccine is manufactured in a culture “bag” that is filled with media and nutrients necessary for cells to grow and divide to numbers that meet the vaccine dose. This one-time use “bag” is completely closed to the outside environment except for valves that connect to lines that pump in additional media and nutrients. This closed system environment reduces the risk of the vaccine getting contaminated with bacteria and fungi. 
  4. Concentrating Small Doses: The volume of liquid in which cells are manufactured is much too large to give to patients. This machine concentrates the cell dose into smaller volumes that can be safely injected or infused into the patient receiving the vaccine.


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