11PD - Tapping CD4 T cells for cancer immunotherapy

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Poster discussion session
Presenter Else Marit Inderberg
Citation Annals of Oncology (2016) 27 (suppl_8): viii2-viii4. 10.1093/annonc/mdw526
Authors E.M. Inderberg1, M.R. Myhre1, N. Mensali1, A. Fåne1, K. Lislerud1, G. Kvalheim1, G. Gaudernack2, S. Wälchli1
  • 1Dept. Of Cellular Therapy, Oslo University Hospital- The Norwegian Radium Hospital, 0379 - Oslo/NO
  • 2Section For Cancer Immunology, Oslo University Hospital- The Norwegian Radium Hospital, 0379 - Oslo/NO

Abstract

Aim/Background

T-cell based immunotherapy is an attractive treatment for advanced cancer. Whereas cellular immune responses against tumour 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. Recent findings have highlighted new opportunities for CD4 T cells in cancer immunotherapy.

Methods

From patients that clinically benefitted from treatment with cancer vaccines targeting antigens such as hTERT, survivin and frequent neoantigens such as frameshift mutated TGFβRII we have isolated CD4+ T cells reactive against tumour antigens. Strong T-cell responses against the vaccine or unrelated cancer antigens suggesting epitope spreading correlated to enhanced survival and/or 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 third-party T cells by mRNA electroporation or retroviral transduction and tested for functionality.

Results

Both CD8+ and CD4+ T cells expressing the TCRs produced TNF-α, IFN-γ and had the capacity to kill following co-incubation with their targets. Selecting highly functional CD4+ T-cell clones reactive against tumour-associated or -specific antigens from patients with clinical responses after immunotherapy treatment is a successful method for identifying highly functional HLA class II restricted TCRs for adoptive immunotherapy.

Conclusions

The use of HLA class II-restricted TCRs may be of therapeutic value both in haematopoietic malignancies and in melanoma where tumour cells often express HLA class II. Furthermore, 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.

Clinical trial identification

Legal entity responsible for the study

Oslo University Hospital

Funding

Norwegian Research Council, Southern and Eastern Norway Regional Health Authority

Disclosure

All authors have declared no conflicts of interest.