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ACT regimen results in the in vivo expansion and enhanced activity of these
cytotoxic lymphocytes. Of the 35 melanoma patients treated by adoptive cell ther-
apy in a phase II clinical trial, 18 patients (51 %) achieved an objective response,
with 3 patients exhibiting a complete response (Dudley et al. 2005 ). NCI has identi-
fi ed and characterized a number of melanoma tumor-associated antigens, including
gp100 and MART-1, and has developed a lymphodepleting non-myeloablative regi-
men used for ACT. Transgene and the NCI have collaborated to evaluate new can-
didate cancer vaccines, with the objective to assess the boosting effect of the
vaccination on the lymphocytes’ activity. These novel vaccines were designed by
Transgene using viral vectors to express melanoma antigens. Such a vaccination has
already demonstrated increased in vivo clonal expansion and maintenance of adop-
tively transferred tumor-antigen specifi c cytotoxic lymphocytes in preclinical mod-
els. The NCI will conduct preclinical evaluation of the vaccines and sponsored a
phase I/II trial. The adoptive transfer of in vitro generated tumor antigen-specifi c
cytotoxic T lymphocytes (CTL) provides a promising approach to the immuno-
therapy of cancer. A phase I study was conducted to test the feasibility, safety, and
survival of adoptively transferred Melan-A-specifi c CTL lines in melanoma patients
and shown to induce clinical tumor-specifi c immune responses without major
adverse effects (Mackensen et al. 2006 ).
Tumor infi ltrating lymphocytes (TILs) already appear to offer signifi cant patient
benefi t and this approach now warrants further development. Genetically engi-
neered T cells offer a means to endow peripheral blood T cells with antitumor activ-
ity and in principle these techniques could allow the treatment of a wide range of
cancers. Genetic engineering also offers the means to endow T cells with new prop-
erties and enhanced functions. Proof-of-principle trials have shown clear responses
with T cell receptor-engineered T cells and this can be built on with further develop-
ment (Hawkins et al. 2010 ).
Epstein-Barr virus (EBV) infection is associated with a heterogeneous group of
tumors, including lymphoproliferative disorders, Hodgkin’s disease, nasopharyn-
geal carcinoma and Burkett’s lymphoma. As these cancers express viral antigens,
they can be treated by ACT strategies relying mostly on in vitro generation and
expansion of virus-specifi c CTL, which can be administered to patients for both
prophylaxis and treatment. ACT with EBV-specifi c CTL is safe, well-tolerated and
quite effective in the case of most immunogenic tumors, egg, post-transplant lym-
phoproliferative disease (Merlo et al. 2008 ).
Combination of Antiangiogenic Agents with ACT
Although ACT-based immunotherapies can achieve cancer regression in animal
models and in up to 70 % of patients with metastatic melanoma, it is possible that
the tumor vasculature impedes the egress of tumor-specifi c T cells, thus hindering
immunotherapy. Disruption of the proangiogenic interaction of VEGF with its
receptor VEGFR-2 has been reported to “normalize” tumor vasculature, enhancing
the effi cacy of chemotherapeutic agents by increasing their delivery to the tumor.
10 Personalized Therapy of Cancer