Marit Renee Myhre has been selected to give a talk at the 17th International Conference on Progress in Vaccination Against Cancer (PIVAC 2017) in Loutraki, Corinth, Greece
She will present our latest work on our new CD4-based therapy, make sure to have a look at the abstract if you want to learn more !
Exploiting CD4 T cells for adoptive cell therapy in cancer
Marit R. Myhre1, Pierre Dillard1, Nadia Mensali1, Sylvie Pollmann1, Gunnar Kvalheim1, Gustav Gaudernack2, Sébastien Wälchli1, Else M Inderberg1
1Department of Cellular Therapy, 2Section for Cancer Immunology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway
T-cell based immunotherapy represents an attractive strategy for the treatment of cancer.
Whereas cellular anti-tumour immune responses have typically been attributed to CD8 T cells, CD4 T cells play a critical role in tumour elimination and the priming and maintenance of CD8 T-cell responses. Combining HLA class I- and class II-restricted TCRs for T-cell redirection may provide a more potent therapeutic effect in adoptive T cell therapy.
Furthermore, HLA class II-restricted TCRs may be of therapeutic value both in haematopoietic malignancies and in melanoma where tumour cells frequently express HLA class II.
We have isolated CD4+ T cells reactive against tumour antigens from patients who experienced clinical benefit from treatment with cancer vaccines targeting universal tumourantigens and frequent neoantigens. Strong T-cell responses against the vaccines or unrelated cancer antigens suggesting epitope spreading correlated with enhanced survival and tumour regression in late stage cancer patients.
These HLA class II restricted T-cell clones recognised target cells loaded with long peptides or protein and for some CD4+ T cell clones we could also show direct tumour recognition.
TCRs were expressed in expanded donor T cells by mRNA electroporation or retroviral transduction and found functional in both CD8+ and CD4+ T cells producing TNF-α, IFN-γ with the capacity of target cell killing.
We also show preliminary in vivo data for one of our broadly applicable TCRs recognizing a universal antigen, hTERT, presented on one of the most frequent HLA alleles, HLA-DP4.