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Abstract Book 2010 - CIMT Annual Meeting

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037 Aarntzen | Immune monitoring<br />

Skin-derived functional specific Tcells predict clinical outcome<br />

upon DC vaccination in stage III and IV melanoma patients<br />

Erik Aarntzen 1,2 , Annemiek de Boer 1 , Nicole Meeusen-Scharenborg 1 , Danita Schuurhuis 1 ,<br />

Gerty Schreibelt 1 , Joost Lesterhuis 1,2 , Hans Jacobs 1 , Michelle van Rossum 3 , Carl Figdor 1 ,<br />

Gosse Adema 1 , Kees Punt 2 , Jolanda de Vries 1<br />

1<br />

Centro de investigación médica aplicada (CIMA)<br />

2<br />

Bristol Myers-Squibb Pharmaceutical research institute, Princeton, NJ<br />

3 Sidney Kimmel Cancer Center. Johns Hopkins Medical School. Baltimore, BA<br />

80<br />

Purpose: To improve immunotherapy against<br />

cancer, tumor-specific immunomonitoring is essen-<br />

tial. In this study, we analyze the predictive value of<br />

T cell cultures from Delayed Type Hypersensitivity<br />

(DTH) skin sites as monitoring tool after dendritic<br />

cell (DC) vaccination in melanoma patients.<br />

Patients and methods: In our ongoing trials, HLA-<br />

A2.1 positive stage III and IV melanoma patients<br />

are vaccinated with mature DC loaded with the<br />

tumor associated antigens gp100 and tyrosinase.<br />

After vaccination, tumor-specific response is routinely<br />

evaluated in blood and cultures from DTH<br />

infiltrating lymphocytes (DIL).<br />

Results: Almost all stage III and IV patients show<br />

both proliferative and humoral responses to the<br />

control antigen KLH. Tumor-specific CD8+ Tcells<br />

are rarely detected in peripheral blood (6 out of 73<br />

patients tested). In the vast majority of patients,<br />

sufficient cell numbers are obtained from DIL cultures<br />

for tetramerstaining and functional analysis.<br />

We show a strong predictive value of the presence<br />

of functional specific CD8+ Tcells in DIL cultures<br />

for favorable clinical outcome in both stage III<br />

(n=75) and IV (n=85) melanoma patients.<br />

Conclusion: Our findings show that the presence<br />

of functional tumor-specific Tcells from DTH skin<br />

biopsies highly predict clinical outcome.

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