Recherche clinique: Transfert adoptif de lymphocytes T et vaccination dans le traitement des patients atteints d’un mélanome de stade 4

Professional info

- Despite extraordinary results with adoptive cell transfer in melanoma patients, further optimization for this treatment regimen is desired to achieve maximal benefit.
- Initial (promising) data is required to receive funding from Dutch Cancer Society, KWF Kankerbestrijding and the Landsteiner stichting.
- A 2-year financial support allowed to gather more data about the feasibility of an autologous boost vaccine after adoptive transfer of TIL and a clinical trial is prepared to evaluate the safety.
- Additional data was sufficient to achieve more external funding. The temporary support of the Anticancer Fund ensured the continuation to establish a possible improvement for adoptive cell therapy.

 

Location: Leids Universitair Medisch Centrum, clinical oncology, Leiden, Netherlands
Collaboration: Dr. Ir. E.M.E. Verdegaal en Prof. Dr. S.H. van der Burg

 

Why did we choose this project?

T-cells that have penetrated the tumour are referred to as tumour-infiltrating lymphocytes (TIL). Adoptive T cell transfer (ACT) of autologous TIL is still one of the most successful treatments today for advanced metastatic melanoma patients. Clinical effectiveness of adoptively transferred T cells could possibly be further improved by vaccination. This promising project required “seed” financial support to obtain initial data in order to obtain funding from KWF kankerbestrijding.

 

The aim

The project aims to expand tumor specific T cells by in vitro stimulation of blood derived T cells with irradiated autologous tumor cells. ACT of these T cells in combination with low dose interferon-alpha (IFN-a) to precondition the patient and sustain T cell activation in vivo results in 50% clinical response. Results might further improve if T cells become boosted in vivo by vaccination with irradiated autologous tumor cells together with Hiltonol, a TLR3 agonist, to stimulate the appropriate immune response.

 

How did we approach the project?

Protocols to generate autologous melanoma cell lines and tumor reactive T cells were optimized.
A phase I/II clinical trial was prepared to evaluate the feasibility and safety of ACT followed by autologous tumor cell vaccination combined with Hiltonol.

 

What did we find?

Melanoma cell lines cannot be established in half of the patients despite using optimal medium. Alternatively, primary tumor cell cultures instead of tumor cell lines can be used to obtain tumor reactive T cells from blood derived white blood cells.

At current there are three options for the future treatment protocol. Patients can receive TIL or tumor reactive T cells from blood derived white blood cells stimulated with autologous tumor cells or one of these two combined with an autologous tumor vaccine and Hiltonol. Responding patients received T cells recognizing private/mutated antigens which did not react against autologous control cells.

 

Based on what we learnt, what’s the message we want to give to the public?

The temporary support of this research project allows to further develop a very promising treatment.  The additional data generated during this 2-year project were sufficient to receive funding of Dutch cancer society, KWF Kankerbestrijding and the Landsteiner stichting (LSBR). The continuation of this project is a valuable achievement of ACF.