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
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.
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
This poses manufacturing challenges because, in general, there is no
commercial model for the manufacture and marketing of a customized product,
“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.
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
“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.