Program leaders

• B.A.C. Dijkmans (Rheumatology)
• G.J. Ossenkoppele (Hematology)
• G.J. Peters (Medical Oncology)
• S. Senan (Radiotherapy)
• H.M.W. Verheul (Oncology)

The CCA/V-ICI program 4 encompasses translational research within the field of oncological and immune-mediated, non-oncological diseases and focuses on the following two research lines:

• Targeted therapy, including radiotherapy, surgery and systemic therapy
• Immunotherapy

The major aim of the program is to explore potential synergies when innovative and targeted therapies are combined with classical radiotherapy and chemotherapy  for both oncological and immunological diseases. This  includes pre-clinical evaluation and clinical application of the new generation of the so-called molecular targeted therapies against novel cellular targets, anti-angiogenesis agents and the pharmacological optimalization of conventional cytotoxic and antirheumatic drugs. Identifying novel targets and in-house drug discovery for which (pharmaco)genomics and proteomics, as well as  investigating mechanisms of drug resistance are a key focus. Imaging and disease profiling will be performed in close collaboration with CCA/V-ICI program 3. Preclinical and early studies in radiotherapy currently focus on combining radiotherapy with radiosensitizing molecular targeted therapies, with the aim of developing experimental arms for future clinical trials. Another active area of research is the optimisation of 4-dimensional image-guided approaches that aim to improve local control and reduce normal tissue toxicity.

The program encompasses the work many Clinical Departments involved in clinical cancer research. It remains a fact that a significant number of them do not actively focus on clinical translational research, but are instead major referral centers for distinct immunological and oncological diseases. In the case of the latter, the clinical activities of such Departments have led to recognition as national referral centers for some disease types, stimulated  patient accrual to novel clinical trials, access to new drugs, facilitated strong contacts with pharmaceutical companies, and resulted in key clinical publications. It is expected that the contributions of such clinically-orientated departments will continue to add to high-quality output of program 4

The research line Immunotherapy investigates new immunotherapeutic approaches for the treatment of rheumatoid arthritis and other immunological disorders as well as oncological disorders. For example a major focus of immuno-therapy of malignant disorders is evaluating the role of vaccination in the adjuvant and primary settings. Improved survival rates are now achievable for a number of common malignancies by using combined modalities. Collaboration with program 2 has been initiated and will be broadened in next years.

Perspectives

In the next five years, specific patient-tailored therapies will be developed in a range of oncological and immunological diseases. These therapies will be directed to defined cellular- and tumor environment targets and characterization of genetic polymorphisms in order to prevent toxicity and increase anti-tumor or anti-inflammatory activity. The new techniques will be used in concert  with image-guided controlled radiotherapy and surgery to further refine the concept of personalized tailored therapy. The existing expertise of both the VUMC micro-array facility and the VUMC OncoProteomics Laboratory will form a solid extension to faciclitate these aims. Furthermore, effective dendritic vaccines will be developed and evaluated in clinical studies of various malignancies. By exploiting the existing expertise within the V-ICI in immune effector-targeted approaches in cancer therapies, novel immune-therapies willl also be explored in treating auto-immune disorders

Research aims for the coming 5 years

• Increase translational research with a focus on the early clinical application of relevant discoveries. The process of clinical evaluation can range from early studies of feasibility and toxicity to the validation of efficacy of new techniques, drugs or vaccines.
• Focus on targeted therapy in all its forms, including pharmaceuticals, radiation, immunotherapy and surgery, directed towards the deregulated cell (arising from either malignant or immunological dysfunction) so as to improve efficacy and minimise collateral damage to normal tissues.
• In the clinical departments that are more heavily involved in clinical cancer research in Phase I,II and III trials, every effort will be made to ensure that such trials are better integrated into existing lines of translational and immunological research.
• Exploit the existing expertise in both immunology, oncology  and imaging in order to develop novel therapeutic approaches.

Collaboration

In VUMC
A large number of departments are involved in program 4. Translational researchers in program 4 are now working in close contact with more fundamental/pre-clinical researchers from program 1-3 in order to allow the transition of bench-to-bedside research. Information about the research meetings of all the departments in program 4 are now disseminated on the V-ICI website to stimulate cooperation among the different departments. It is anticipated that this will increase the merging of oncological and immunological research.

Outside VUMC
Researchers in program 4 have partnerships with industry and with other academic centers in and outside the Netherlands. This will be further exploited in the coming years.