Volume 2 Supplement 2

Abstracts from the 1st Immunotherapy of Cancer Conference (ITOC1)

Open Access

P68. A new EGFR - EpCAM bispecific antibody enhances the efficacy of adoptive T-cell therapy in a murine gastric tumour model

  • S Kobold1,
  • J Steffen1,
  • S Grassmann1,
  • R Castoldi2,
  • J Schmollinger1,
  • C Sustmann2,
  • G Nierderfellner2,
  • C Klein2,
  • C Bourquin1 and
  • S Endres1
Journal for ImmunoTherapy of Cancer20142(Suppl 2):P42

https://doi.org/10.1186/2051-1426-2-S2-P42

Published: 12 March 2014

Background

A limiting step for adoptively transferred tumour-specific T cells is their recruitment from the blood circulation to the proximity of tumour cells and subsequent engagement in direct tumour cell contact. We hypothesised that a bispecific antibody recruiting T cells to a target antigen on tumour cells could enhance T-cell-tumour interaction and thus increase the efficacy of adoptively transferred T cells.

Material and methods

A new bispecific murine IgG2a antibody (BsAb) was generated that recognises EpCAM as a tumour antigen and truncated EGFR (D-EGFR) as an inert surface marker protein on transduced T cells. T cells from transgenic mice for TCR specific for the SV40 large T antigen (TCR-1) were retrovirally transduced with D-EGFR. S.c. tumors were induced in C57Bl/6 mice by injecting mGC8 cells derived from a syngeneic large T antigen expressing EpCAM-positive gastric tumor.

Results

In vitro, the BsAb increased (4-fold) binding of transduced T cells to EpCAM positive tumour cells. In the presence of the BsAb, tumour-directed T cells efficiently lysed EpCAM-positive cells (83 % at a 10:1 effector to target ratio). In vivo, the antibody reached EpCAM+ tumour cells as evidenced by immunofluorescence. mGC8 tumour-bearing mice were treated twice with a combination of the BsAb and transduced TCR-I T cells. Tumour growth was significantly reduced for over 30 days (n=12) compared with control groups (transduced T-cells or BsAb alone) and survival was prolonged by > 30 days (p<0.001).

Conclusions

Co-administration of a BsAb bridging adoptively transferred tumour-specific T cells via an inert surface molecule to a tumour-associated surface antigen enhances the efficacy of therapeutic T cell transfer.

Authors’ Affiliations

(1)
Division of Clinical Pharmacology
(2)
Roche Diagnostics GmBH, Discovery Oncology

Copyright

© Kobold et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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