Joshua Brody, MD

Instructor, Division of Oncology, Department of Medicine, Stanford University

Mantle cell lymphoma (MCL) is a relatively rare, aggressive form of non-Hodgkin lymphoma.  To date there is no broadly recognized standard of care for the treatment of MCL.  Conventional therapies, such as high-dose chemotherapy, monoclonal antibodies, stem cell transplants, and various combinations of these treatments, can successfully destroy lymphoma, however, some residual cancer cells remain—generally resulting in the recurrence of MCL.  For this reason it is imperative to develop novel ways to rid the body of this residual lymphoma.

In 2007, Joshua Brody, MD, (Instructor, Division of Oncology, Department of Medicine, Stanford University) received a three year Clinical Investigator Career Development Award from the Lymphoma Research Foundation to study cancer vaccines as a way to eliminate residual lymphoma and significantly improve cancer-free survival among patients with MCL.

A patient-specific or custom-made cancer vaccine is an immunological treatment based on the genetic makeup of an individual patient’s tumor. They are non-toxic and routinely given to a patient during a period of minimal disease—for example, after the patient receives chemotherapy. The vaccine works by enlisting a patient’s own immune system to attack their cancer. Many researchers have been studying cancer vaccines, but have had mixed results.

Under the guidance of Ronald Levy, MD, (Professor and Chief, Division of Oncology, Stanford University School of Medicine) Brody and his colleagues are testing a new method for administering vaccines—by giving the vaccine after a patient receives chemotherapy and an autologous stem cell transplant (ASCT).

Within the treatment protocol, patients first undergo a biopsy to obtain tumor cells that will be used to develop the vaccine. After the biopsy, patients then receive chemotherapy (RB-hCVAD) followed by a “preliminary” vaccine. The body’s immune system reacts by producing anti-lymphoma immune cells (primed T-cells) which are harvested from the patient’s body two weeks later—using a medical technique called leukapheresis—and frozen. Patients then receive high-dose chemotherapy and an ASCT.

According to Brody, this is an ideal time to administer a vaccine because the chemotherapy has destroyed the majority of lymphoma cells and wiped out the body’s immune cells. “Secretly, this is a huge opportunity. At this point, the patient’s immune system is a clean slate and if vaccinated against cancer now, the immune system has the opportunity to re-grow as an anti-cancer immune system,” says Brody.

After the ASCT, patients receive an infusion of the vaccine and some of their previously harvested anti-lymphoma immune cells to destroy any remaining residual lymphoma. Booster doses of vaccine are also given three and six months post-ASCT.

To date, this treatment method has had tremendous success in eliminating even large lymphoma tumors in animal models. Brody’s next step will be to test the method in a clinical trial.   “This ‘immunotransplant’ approach has increased the power of lymphoma vaccines perhaps 10-40 fold. Since our recent clinical trials of lymphoma vaccines in the usual (non-transplant) setting have demonstrated clinical responses in a minority of patients, we hope that clinical trials of immunotransplant will similarly show a great increase in anti-cancer efficacy.”

When asked what advice he would give to younger physician-scientists getting started in the field, Brody replied, "Get yourself a great mentor who believes in your ideas and believes in you.  Preferably one who has an excellent grasp of the big picture and all the little details that make it up.  I've been fortunate to have some good ideas about how to improve on immunotherapy for lymphoma, but without a great mentor, I would never have had the chance to bring these ideas to life."