4PD - A universal killer T-cell for adoptive cell therapy of cancer

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Poster Discussion session
Topics Cancer Immunology and Immunotherapy
Presenter Sébastien Wälchli
Citation Annals of Oncology (2015) 26 (suppl_8): 1-4. 10.1093/annonc/mdv513
Authors S. Wälchli1, E.M. Inderberg1, J.H. Myklebust2, G. Skorstad1, M.R. Myhre1, A. Faane1, G. Gaudernack2, G. Kvalheim1
  • 1Cellular Therapy, Oslo University Hospital, 0310 - Oslo/NO
  • 2Ikf-cancer Immunology, Oslo University Hospital, 0310 - Oslo/NO

Abstract

Aim

T cell-based therapy has generated remarkable remissions in hard-to-beat cancers and represents a large part of innovations in immunotherapy.

Methods

Adoptive T-cell transfer (ACT) was initiated almost 20 years ago and is a labour intensive method. To overcome the frequent limitation of insufficient numbers of tumour-reactive T cells, the patient T cells are modified to express tumour-specific T-cell receptors (TCR). In order to avoid GvHD, only the patient's own T cells or those of an HLA-matched donor can be used. The infusion of T cells involves long and heavy procedure: the isolation, the activation, the expansion and the transformation of the T cells. In addition, the quality of the patient T cells and the efficiency of the TCR transfer affect the outcome of the treatment. Finally, the therapeutic TCR sometimes mispairs with the endogenous TCR, which can lead to off-target redirection. A way to simplify the therapy in order to treat a larger number of patients would be to use Natural killer (NK). NK cells have the capacity to recognize some cancer cell types and kill them. However, the isolation and reinfusion of patient NK cells has proven difficult as they are challenging to expand and transform. Nevertheless, the NK cell line, NK-92, has retained its killing capacity and can easily be manipulated. Furthermore, NK-92 has been approved by the FDA for clinical trials in cancer patients and has so far been shown to be safe. NK-92 cannot recognize specific tumours but this can be overcome by introducing an antigen receptor, such as a CAR or a TCR.

Results

Our innovation is the transformation of NK-92 into T cells by making them able to express a therapeutic TCR, recognize a malignant cell and kill it. This is a perfect combination of the inherent killing activity of the NK cells and the specific targeting of cancer antigens through TCR. We named these cells Universal Killer-92 (UK-92). We have now shown in vitro that these UK-92 are as specific and potent as T cells to destroy cancer cells carrying a TCR specific for a cancer antigen.

Conclusions

We can anticipate that this technology, if proven efficient in vivo, will speed up ACT and reduce its cost.

Clinical trial identification

NCT00900809 and NCT00990717

Disclosure

G. Gaudernack: Is CSO of Ultimovacs and scientific board member of different biotech startup companies

. All other authors have declared no conflicts of interest.