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Monitoring of tumour antigen specific CD4+ T cell responses

preclinical study dataset

We obtained data from an in vitro system to study ex-vivo responses able to detect bona fide in vivo primed CD4+ T cells.

We focused on the monitoring of tumour antigen specific CD4+ T cell responses. We select the following tumour associated antigens:
i) the E6 and E7 proteins of human papilloma viruses,
ii) the carcinoembryonic antigen (CEA) and
iii) the tumour specific antigen MAGE-A3.

We investigated spontaneous CD4+ T cell responses to these antigens in normal donors and in patients with high-grade cervical lesions, pancreas adenocarcinoma and advanced melanoma. HPV-18 E6 specific CD4+ T cells were found in a high percentage of patients with cervical lesions and we showed that the quality of the response (i.e. the level of IFN-? produced) could predict the clinical outcome after surgery. CEA specific CD4+ T cells were found both in normal donors and in patients but CD4+ T cells from the patients compared to normal donors showed impaired IFN-gamma production. MAGE-A3 specific CD4+ T cells were found also in a high percentage of melanoma patients but CD4+ T cells showed an unpolarized or Th2 skewed phenotype. We have optimized the MAGE-A3 peptides to load onto HLA-DR*1101 tetramers.





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