General Area of Research
Immunotherapy is making major progress in the clinic and treatment with checkpoint inhibition (CI) results in significant increase in the overall survival among patients with advanced malignant melanoma. Yet, the majority (>50 %) of patients are not helped, why there is a need for improvements by novel combinations and by predictive biomarkers. Administration of tumor infiltrating lymphocytes (TIL) combined with after low dose chemotherapy has been reported to result in long-lasting clinical responses in 20% of the treated patients in patients with metastatic melanoma.
Ongoing research projects
A Phase I study with TIL combined with a Dendritic cell (DC) vaccine in advanced malignant melanoma patients is ongoing as an improved continuation of our published “First-in-man” pilot study. Several complete and long-lasting responses according to RECIST 1.1 have been observed, motivating an analysis of the responsible T cell clones and a search for antigens recognized by infused T cells, focusing on the role of missense mutations as “neoantigens”. A search for predictive biomarkers has shown promising results, and the presence of monocytic Myeloid Derived Suppressor Cells (moMDSC) was shown to predict poor response to CI.
Conclusion from our research
Cell therapy can result in complete clinical responses also in patients who are not responding any longer to checkpoint therapy. Our project has revealed a critical role for moMDSC in conferring resistance to immunotherapy and as predictive biomarkers for clinical response.
Research Funding
- The Swedish Cancer Society
- Swedish Medical Research Council
- ALF-Project grant from the Stockholm City Council
- Cancer Society in Stockholm
- Knut and Alice Wallenberg foundation
- Torsten Söderbergs Stiftelse