67P - Generation and characterization of cord blood derived T cells redirected with a TCR targeting E7/HLA-DR4 complex (67P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Palliative Care
Palliative and Supportive Care
Presenter Chrystel Marton
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors C. Marton1, P. Letondal1, M. Deschamps1, C. Ferrand1, O. Adotevi2, C. Borg2, J. Galaine1, Y. Godet1
  • 1Thérapeutique Immuno-moléculaire Des Cancers, UMR1098, 25020 - Besançon/FR
  • 2Medical Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR

Abstract

Background

Adoptive T cells transfer is a promising cancer treatment. However, despite the impressive success of CD19-CAR T cells, its transposition to solid tumor is challenging. The selection of safe targets and the requirement of tumor infiltration are two main hurdles. In HPV related cancers, an oncoviral protein such as HPV-E7 is an attractive and safe target, and there are clinical evidences of the effectiveness of E7 targeted therapies (Kenter GG et al. 2009). TIL trials in melanoma have revealed that in vivo persistence of infused cells is required to achieve treatment efficacy. In this view, less differentiated T cells such as stem memory T cells or central memory T cells have a superior in vivo persistence. Cord blood is a source of more naive T cells compared to peripheral blood and could be used to develop novel immunotherapeutic strategies.

Methods

A E7/HLA-DR4 specific TCR has been isolated from a cancer patient and retroviral particles encoding this TCR has been produced. Cord blood and peripheral blood T cells were isolated and activated before the retroviral transduction with a vector encoding for this TCR. We then evaluated by flow cytometry the differentiation profile and functions of cord blood and peripheral blood transgenic T cells.

Results

Functional assays revealed that both transduced CD4 and CD8 T cells were reactive against HLA-DR4+ BLCL pulsed with the E7-derived peptide. Transduction efficiency was slightly lower for cord blood T cells. As expected, cord blood transduced T cells show a higher rate of CD4 and CD8 T memory stem cells (CD45RA+CD45ROlowCD95+CCR7+) than peripheral blood T cells. This more naive phenotype is associated with lower effector functionalities (interferon-γ secretion and degranulation).

Conclusions

In conclusion, cord blood T cells could be redirected with a TCR targeting E7/HLA-DR4 complex and are less differentiated than their peripheral blood counterparts. This profile could allow them to proliferate and persist longer in vivo, while enhancing their antitumor capacities. These results point out the interest of cord blood as a source of cells for adoptive cancer immunotherapy using receptor-engineered T cells.

Clinical trial identification

Legal entity responsible for the study

UMR1098

Funding

None

Disclosure

All authors have declared no conflicts of interest.