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Personalized Vaccine for Follicular Lymphoma
Follicular lymphoma is considered incurable, although cyclophosphamide, doxoru-
bicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential
remissions. In one study, patients with follicular lymphoma were vaccinated peri-
odically for more than 2 years with autologous lymphoma-derived idiotype protein
vaccine (Inoges et al. 2006 ). The vaccine presents a tumor protein to the patients in
such a way that their immune systems recognize it and destroy any cells bearing that
protein. Idiotypic vaccination induced a specifi c immune response in the majority of
patients with follicular lymphoma. Specifi c immune response was associated with a
dramatic and highly statistically signifi cant increase in disease-free survival. This is
the fi rst formal demonstration of clinical benefi t associated with the use of a human
cancer vaccine. Such clinical trials cannot be randomized as each patient serves as
his or her own control. A second remission longer than the fi rst would be an indica-
tion of effi cacy.
Companion Diagnostic for Treatment of Lymphoma with Adcentris™
Seattle Genetics and Takeda’s Millennium are developing Adcetris™ (brentuximab
vedotin) jointly. Adcentris (brentuximab vedotin) is an antibody-drug conjugate
(ADC), which comprises an anti-CD30 MAb attached by a protease-cleavable
linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utiliz-
ing Seattle Genetics’ proprietary technology. The ADC employs a linker system
that is designed to be stable in the bloodstream but to release MMAE upon inter-
nalization into CD30-expressing tumor cells. Adcentris was granted accelerated
approval by FDA in 2011 for treating 2 types of lymphoma: (1) relapsed Hodgkin
lymphoma after failure of autologous stem cell transplant or after failure of at least
two prior multi-agent chemotherapy regimens; and (2) systemic anaplastic large
cell lymphoma after failure of at least one prior multi-agent chemotherapy regi-
men. It is also in development for a range of other CD30-expressing lymphoma and
non- lymphoma malignancies, both as monotherapy and in combination with
chemotherapy.
As part of their ongoing clinical development program for the drug, Millennium
and Seattle are planning two phase III studies that will incorporate the use of a com-
panion diagnostic, although it is currently not required. One trial will involve
patients with CD30-positive cutaneous T-cell lymphoma (CTCL), and the other
patients with CD30-positive mature T-cell lymphomas (MTCL). Although the iden-
tifi cation of CD30 expression and its role in the diagnosis of Hodgkin lymphoma
and systemic ALCL is well established, CD30 expression in other malignancies is
more heterogeneous. Under terms of their collaboration Seattle retains US and
Canadian commercialization rights to the product, and Takeda has rights to com-
mercialize in the rest of the world. The fi rms are funding development costs on a
50:50 basis worldwide, except in Japan, where Takeda has sole responsibility for
developing Adcentris.
10 Personalized Therapy of Cancer