#immunotherapy – Blog about neuroblastoma research

SFI Technology Innovation Development Award

An interesting idea or research question is always motivational. But it is a sketch till you get means to answer them. We, scientists, have to shape them into a proposal showing that we know limitations and have plans B & C if things go differently to planned. Then we apply for funding here and there… and many many times. The number of rejections makes us stronger – I hope. But one day, the idea may hit it right. So, it has happened to me recently and this SFI Award brings so needed fuel to study neuroblastoma.

The development and approval of new oncology drugs are very slow processes. This is mainly due to the big differences in the physiology of cancer cells grown on plastic and in the native microenvironment. Tissue engineering of tumour systems has a great potential to bridge this gap. This Award will help to advance our 3D tissue-engineered of neuroblastoma, that can be used in testing new drugs and new combinations of existing drugs.

In particular, we will adapt the 3D model to screen different immunotherapies. This treatment option is very attractive both for adults and children because of its specificity and reduced side effects compared to chemotherapy, the current standard of care.

This Award will help my team to get a better understanding how neuroblastoma cells interact with the body environment, particularly with the immune system and how we can use the knowledge to develop new treatments and improve the patient outlook.

What lessons have been learnt?

Today is the final day of the Third International Cancer lmmunotherapy Conference. The meeting was run at the Rheingoldhalle Congress Center in Mainz/Frankfurt, Germany from September 6-9, 2017. More than 500 people attended this meeting.

The focus of the scientific program was on “Translating Science into Survival”. Talks covered the challenging areas in cancer immunology and immunotherapy. The full list of topics can be found in the meeting program.

At the moment cancer immunology and immunotherapy is a hot topic in the next generation of anti-cancer therapies. Lots of attention is given to checkpoint immunodrugs as it was proven by the prevalence of talks on this subject in the program. Indeed, this drug has great potential, but at the same time, it is not universal. About 50% of patients do not benefit from it.

What lessons have been learned from the talks:

Checkpoint immunotherapies are the main stream
Not all cancer patients would respond to immunodrug
Genetic landscape of a tumour and/or the patient may contribute to this, thus making beneficial to check genetics for this type of treatment
Immunodrugs work better in combination with conventional therapies such as chemotherapy.
The immune system can be tuned by a drug, but it will switch on compensatory mechanisms to balance the intervention.
Lots have to be studied further

Father of Chemotherapy and Cancer Immunology

I was giving a talk at Georg-Speyer-Haus Institute for Tumour Biology and Experimental Therapy yesterday. The aim of my visit was to establish collaboration with Prof Daniela Krause, who is the expert in bone marrow microenvironment and targeted therapies. She took me to the Institute museum that keeps the history of this place and phenomenal researchers used to work there.

This research institute was established in 1904 to support work of Paul Ehrlich, its first director and funded by the private foundation “Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus”. Paul Erlich is the Father of the chemotherapy concept originally developed to treat diseases of bacterial origin. He reasoned that there should be a chemical compound that can specifically target bacteria and stop its growth. He developed Salvarsan, the most effective drug for treatment of syphilis until penicillin came onto the market.

Paul Erlich is also known for his contribution to cancer research. He and his colleagues actively experimented on how tumour originates and spread. They also tried to understand how immune system can beat cancer applying vaccination concepts.

Paul Erlich’s Lab back then. Now it is a museum

Paul Erlich and Ilya Mechnikov were jointly awarded The Nobel Prize in Physiology or Medicine for his “work on immunity” in 1908.

Tumour immunology and immunotherapy for neuroblastoma

The main challenge in treating high-risk neuroblastoma is to stop or control tumour spread and development of resistance to multiple chemotherapeutic drugs. Immunotherapy is one of the recent advances in our understanding how our immune system handles body invaders such as virosis, bacteria and now tumour cells. Immunotherapy holds great promise as a treatment option for neuroblastoma as well as for many adult cancers owing to the specificity of immune effector cells targeted to a tumour. Another advantage is a potential reduction in the systemic side effects observed with other forms of treatment.

This video ‘Tumour immunology and immunotherapy’ will give a brief overview of the basic concepts.

Immunotherapeutic approaches for neuroblastoma include the use of chimeric antigen receptor (CAR) T cells against both L1-CAM and ganglioside 2 (GD2) cell surface antigens to promote host antitumor response. Anti-GD2 antibodies bind GD2 and cause cell death by activating both complement-dependent cytotoxicity (CDC) and AB-dependent cellular cytotoxicity (ADCC) from natural-killer cells.