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Follicular lymphoma vaccine specifically targets tumor cells, offers individualized treatment
There is ample research ongoing of immunotherapies and cancer vaccines, but the furthest along in the pipeline is a follicular lymphoma vaccine that is making its way to the FDA and other regulatory agencies in Europe and Canada.
BiovaxID (Biovest) consists of hybridoma-derived autologous tumor immunoglobulin idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH), which is administered with granulocyte-monocyte colony–stimulating factor.
“The vaccine is unique because it is customized from each patient’s tumor cells,” Larry Kwak, MD, PhD, professor and chairman of the department of lymphoma/myeloma at The University of Texas MD Anderson Cancer Center, said in an interview. “What we’re after is a specific protein made by the tumor cell. This protein is a target that is uniquely expressed by the tumor cell and no other cells in the body. What that means is that it should be the magic bullet, and there should be little or no collateral damage.”
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The phase 3 trial was completed last year, and the results were published in the Journal of Clinical Oncology. The study included 117 patients who were randomly assigned 2:1 to the Id-KLH plus GM-CSF or to a control arm of KLH plus GM-CSF. Before being given the vaccine, the patients all had a complete response to chemotherapy with prednisone, doxorubicin, cyclophosphamide and etoposide. The DFS was 44.2 months for the vaccine arm vs. 30.6 months for the control arm, at a median follow-up of 56.6 months.
Ultimate specificity
The immunotherapies that are approved, such as ipilimumab (Yervoy, Bristol-Myers Squibb), are still associated with adverse effects because they are not entirely specific, Kwak said. Most have targets on tumor cells, but they also have targets on normal cells.
This is not the case for the follicular lymphoma vaccine, Kwak said, adding that this vaccine is unique in that it is completely specific. There is no expression of the targeted protein on any cell in the body except for the patient’s tumor.
This poses manufacturing challenges because, in general, there is no commercial model for the manufacture and marketing of a customized product, Kwak said.
“I’m confident that the industry will catch up, and we’ll develop commercialization models that would support these types of individualized products because they are effective,” he said.
Future plans
There are two possibilities for the use of the follicular lymphoma vaccine, Kwak said. The first is a combination, sequential therapy that starts off with chemotherapy to induce complete remission, as a minimal disease state is the ideal setting for cancer vaccines. After chemotherapy, the vaccine would be administered to knock out residual tumor cells.
The second possibility for use of the vaccine is as a single agent in patients with low-grade tumors who are not symptomatic and have lower tumor burdens, Kwak said. The principle is the same as with the first possibility. The difference is that patients do not need chemotherapy to a lower tumor burden because they already have a lower tumor burden.
Kwak said follow-up studies are being planned for after the drug is approved by the FDA that include rituximab (Rituxan; Genentech/Idec), which was not a part of the chemotherapy regimen in the trial. One trial will look at maintenance therapy with rituximab and the vaccine compared with rituximab alone.
“This vaccine opens new doors because, as great a drug as rituximab is, even in combination with chemotherapy, it does not cure patients with follicular lymphoma,” Kwak said. “The ultimate goal of curing patients is still an unmet need. This vaccine, in combination with chemotherapy and rituximab, has the potential to achieve that goal of curing patients.” – by Emily Shafer
For more information:
- Schuster SJ. J Clin Oncol. 2011;29:2787-2794.
Disclosure: Dr. Kwak is a consultant for Biovest International and a founder of the company XEME.