Abstracts for the 25th Annual Scientific Meeting of the International ...

Abstracts J Immunother Volume 33, Number 8, October 2010
Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme
that are implicated in suppressing T cell immunity in normal and
pathological settings. Expression of IDO has been shown to induce T
cell anergy and/or the generation of adaptive regulatory T cells. In
cancer patients IDO is expressed within the tumor itself as well as in
antigen-presenting cells in tumor-draining lymph nodes, where it
promotes the establishment of peripheral immune tolerance to tumor
antigens. Recently, we showed that IDO derived peptides are subject
to cellular immune responses. Hence, cytotoxic T cell reactivity
against the IDO derived peptide IDO5 (sequence) restricted by HLA-
A02.01 are present in peripheral blood as well as in the tumor
microenvironment of cancer patients. We demonstrated that these
IDO reactive T cells are indeed peptide specific, cytotoxic effector
cells. IDO reactive T cells are able to recognize and kill tumor cells
including directly isolated AML blasts as well as IDO-expressing
dendritic cells, that is one of the major immune suppressive cell
populations. Consequently, IDO may serve as an important and
widely applicable target for anti-cancer immunotherapeutic strategies.
Methods: To test this notion fourteen patients with incurable
stage III-IV NSCLC off chemotherapy is included in this study.
Further inclusion criteria: PS (0-1), at least one measurable lesion
in CT-scan, and acceptable laboratory values. Patients are
administered bi-weekly IDO vaccinations subcutaneously, and
undergo CT-scan evaluation after 6 vaccinations. In the absence of
progression, patients receive monthly vaccination thereafter until
progression. Primary end points are safety and toxicity. Secondary
end points are immunological and clinical response.
Results: The study is approved by the Danish health authorities
and registered at www.clinicaltrials.gow, and patient inclusion is
ongoing. Preliminary data on toxicity and immune parametres will
be presented.
Conclusion: We assess vaccination against the IDO enzyme as a
potential target for anticancer treatment. IDO is expressed in
cancer cells and antigen presenting cells; and the vaccination
against IDO expressing cells is therefore two-sided. Safety and
toxicity are primary goals.
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