Elke Jäger, II.Medizinische
Klinik, Hämatologie – Onkologie, Krankenhaus Nordwest, Frankfurt
NY-ESO-1 belongs to the group
of `Cancer – Testis´ antigens, which are expressed in different types of cancer
and normal germ line tissues. Compared to other cancer antigens, NY-ESO-1
is one of the most immunogenic antigens inducing spontaneous humoral and cellular
immune responses in a large proportion of patients with NY-ESO-1+ malignancies.
NY-ESO-1 serum antibody is detected in approx. 50 % of patients with advanced
NY-ESO-1+ cancers. Antibody titers correlate with the clinical development
of NY-ESO-1+ disease. Increasing titers are associated with disease progression,
and decreases with tumor regression after surgery or chemo-immunotherapy.
NY-ESO-1 urine antibody was found by Western blot analysis in patients with
high serum antibody titers. The analysis of a larger series of patients with
NY-ESO-1+ cancers showed that detectable NY-ESO-1 serum antibody is closely
associated with measurable NY-ESO-1 specific CD4+ and CD8+ T cell responses.
A number of MHC class I and class II restricted peptide epitopes were identified
that are used as targets for the monitoring of spontaneous or vaccine-induced
NY-ESO-1-specific immune responses. Clinical vaccine trials have been initiated
to evaluate the immunogenicity of different NY-ESO-1 peptides or viral vaccine
constructs. HLA-A2-restricted NY-ESO-1 peptides administered as weekly intradermal
injections have induced strong peptide-specific CD8+T cell responses in the
majority NY-ESO-1-naive patients. The onset and intensity of delayed-type
hypersensitivity (DTH) reactions at the sites of peptide inoculation during
the course of vaccination were found to reflect NY-ESO-1-specific CD8+T cell
responses measurable in the peripheral blood. Modified peptide vaccine schedules
and different NY-ESO-1 viral constructs are currently being evaluated for
the quality of immune responses and clinical correlations. The recent identification
of new NY-ESO-1 peptide epitopes presented by different MHC class I and class
II alleles will broaden the patient population eligible for NY-ESO-1-specific
immunotherapy.