Community Research and Development Information Service - CORDIS


ATTACK Report Summary

Project ID: 305863
Funded under: FP7-HEALTH
Country: United Kingdom

Periodic Report Summary 3 - ATTACK (Adoptive engineered T cell Trials to Achieve Cancer Killing)

Project Context and Objectives:
This is the third publishable summary of the ATTACK Project activities covering the period 01/12/2015 – 26/06/2016.
The ATTACK Project

The ATTACK project involves two multi-centre clinical trials to treat cancer using a form of cell therapy called Adoptive T-Cell Therapy.

The problem we will tackle
It has long been known that immune cells that can recognise and destroy cancer cells are found within the tumour itself. However, in many tumours these cells are not present in large enough numbers to have an impact and that is because cancer cells can often evade detection, thereby preventing the body from raising an army of immune cells to fight the cancer. With Adoptive T-Cell Therapy, we aim to overcome the evasion tactics used by cancer cells to allow the patient’s immune cells to do their job.

Adoptive T-Cell Therapy
Adoptive T-Cell therapy is a promising advance in cancer treatment and involves using a patient’s own immune cells. Similar to stem cell therapy, patient’s own cells are taken, manipulated and then given back to the patient as a treatment. For the ATTACK trials we will collect immune cells from the patient’s blood (T-Cells) and genetically engineer them to target the cancer cells directly. The T-cells are changed in the laboratory into cells called ‘NY-ESO-1 specific T-cells’. This is done by inserting a new gene into the T cells, which we hope will enable them to identify and attack the cancer cells which produce NY-ESO-1 protein. The NY-ESO-1 specific T cells are increased in number by growing them in the laboratory. They are then infused back into the patient along with chemotherapy and another drug called interleukin 2 (IL2).

What we hope to achieve
Building on encouraging clinical results using T-cells to target NY-ESO-1 in melanoma, synovial sarcoma and myeloma, the consortium will undertake two ground breaking Phase II trials. A phase II clinical trial aims to find out whether a new treatment works in particular types of cancer. This involves looking at what side effects a new treatment may cause and how to manage them.

Trial 1:
A Phase II Clinical Trial to Assess the Activity of NY-ESO-1 Targeted T-Cells in Advanced Oesophago-Gastric Cancer. This trial will assess whether we can change a patient’s own immune cells to attack cancer cells affecting the stomach or the oesophagus (food-pipe).

Trial 2:
A Randomized Phase II Clinical Trial to Assess an Optimised Cell Production Process in Patients with Metastatic Melanoma. The aim of this trial is to identify the most effective way to manufacture the NY-ESO-1 specific T-cells and will involve patients diagnosed with advanced melanoma.
There will be two treatment arms in this trial. Patients will be randomly allocated to either one of the two arms:
1. Standard cell manufacture process (used in previous trials and in ATTACK Trial 1).
2. An alternative cell manufacturing process which we hope will improve the quality of the cell products.

ATTACK Partners
This project builds upon previous EU funded pre-clinical projects (ATTACK FP6 and ATTRACT FP7) and comprises a multidisciplinary and translational research group with wide-ranging, relevant expertise. Located across 6 countries in the EU, there are 8 hospital sites, 2 cell manufacturing sites, 6 Universities and 4 companies involved in the project.

Project Results:
Achievements to date:

Clinical Trial
The ATTACK clinical trial I, ‘A Phase II Clinical Trial to Assess the Activity of NY-ESO-1 Targeted T-Cells in Advanced Oesophago-Gastric Cancer’, opened to recruitment in September 2014. To date two patients have received trial treatment including pre-conditioning chemotherapy, NY-ESO-1 T cells and interleukin therapy. The trial is currently paused pending investigation of a patient death at day 46 of the trial. The conclusions of the investigation were that the NY-ESO-1 therapy was unlikely to have directly caused the bone marrow failure seen in the applicable patient through on-target toxicity or mis-pairing. In February 2016, following review of the results, an independent data monitoring committee (IDMC) recommended that recruitment could resume once agreed changes in the protocol were in place.

The European Union has terminated funding of the trial due to the delays seen in the progress of the ATTACK program. The delays were necessary to assess the cause of toxicity prior to continuing the trial. Notice of intent to terminate was received by the project co-ordinator on 23rd May 2016. Termination of the study became effective on 26th June 2016.

Process Development

An aim of this project is to be able to manufacture NY-ESO-1 T-cells (or a similar gene modified T-cell therapy) that can be distributed and used at the time of clinical need. The key requirements are that a suitable starting material (i.e. PBMC apheresis) can be collected in hospital and stored for transport or delayed manufacture, then be GMP manufactured and stabilised for final infusion. The identification of significant quantities of NY-ESO-1 T-cells post infusion at 1 month demonstrate successful engraftment and demonstrate the concept is feasible.

Miltenyi has completed the development of a fully integrated process that allows clinical-grade T-cell selection from blood products, activation of the enriched T-cells and gene-modification via viral vector constructs. Robustness of the automated process using patient material has been verified. Some efforts are still remaining for finalization of the programing of the process (especially protocol generation for batch recording), documentation and definition of QC and IPC tests that are an obligatory part of clinical manufacturing and will have to be completed outside of the project.

Laboratory Monitoring

This involves the development of standardised assays for the efficient monitoring of the two clinical trials.

During Period 3, the following progress was made. The validation report on the flow cytometry method was finalized, entitled: “Detection of T cells gene-engineered with T cell receptor against NY-ESO1 in blood samples, isolated peripheral blood mononuclear cells (PBMC) and cryopreserved PBMC by flow cytometry: assay set up and validation”. Flow cytometry quantitation and assessment of differentiation and activation status of NY-ESO-1 TCR T cells prior to infusion and in patient blood was validated on site on 1) fresh peripheral whole blood samples; 2) freshly isolated PBMC (peripheral blood mononuclear cell) and 3) cryopreserved and thawed PBMC. These assays have been set up using different panels to define distinct T-cell subpopulations, including markers for T-cell differentiation (i.e., CCR7, CD45RA, CD95); T-cell function (e.g., CD107, IFNg, GrB) and exhaustion (e.g., PD1, LAG3, TIM3). Furthermore, laboratory investigations were carried out to elucidate the encountered clinical SAE in the 2 treated patients.

Potential Impact:

The early termination of the funding means that the trial cannot complete and therefore the key clinical outcomes cannot be achieved. The development of appropriate methodologies proceeded as planned but cannot be tested clinically due to the time constraints imposed by the EC.

List of Websites:

Related information


Robert Hawkins, (Chair of Medical Oncology)
Tel.: +44 161 446 8084
Fax: +44 0161 446 3269
Record Number: 189390 / Last updated on: 2016-09-20