Lab for Cancer Immunotherapy

Targeting glycans to improve anti-cancer immunity
Our main goal is to improve immunotherapy for cancer patients by using translational in vitro and in vivo tumor models, performing correlative analysis of patients treated with immunotherapy and conducting early clinical interventional trials (also see link to Medical Oncology).
 
One of our research focus is on the role of glycans and glycan-binding receptors in anti-cancer immunity. Glycans can mediate important interactions with immune cells and manipulation of glycans and glycan-binding receptors (lectins) bear a great potential to improve anti-tumor immune reactions. Glycan-mediated interactions in cancer immunology are significantly underexplored and could be used to improve anti-cancer immunity. Our group has studied the interaction between glycans that contain sialic acids (siaologlycans) and their interaction with Siglec receptors on immune cells and have demonstrated that this pathway can be targeted to augment T cell stimulation and tumor control. Current goals include improvement of cancer immunotherapy by modifying glycans in the tumor microenvironment and glycans of cellular products for adoptive cell therapies including genetically modified T cells.
 
An additional focus of our group is the improvement of immune checkpoint blockade and adoptive cellular therapies by investigating mechanisms and patterns of resistance to these therapies. To this end, we are investigating the tumor microenvironment as well as circulating immune cells in patients undergoing immune checkpoint blockade or adoptive T cell transfer. Identified pathways are further studied in the laboratory for their potential as new targets to improve antitumor immune responses.

Cellular therapy for solid cancers
Adoptive cell therapy with TILs (tumor-infiltrating lymphocytes) for melanoma patients have been developed several years ago at the NIH. Clinical trials have shown high and very encouraging response rates depending on the stage and selection of patients. We have established and expansion protocol for the treatment of melanoma patient refractory to standard immune therapy with checkpoint inhibitors (and BRAF/MEK inhibition in BRAF mutated patients).
 
Our first planned clinical trial  includes an adapted classical expansion protocol and the application of IL-2 after the adoptive TIL transfer. In addition, we will perform a PD-1 blockade after stopping IL-2 treatment to render the tumor microenvironment more permissive for tumor-attacking T cells.
 
Our program will enable us to expand this treatment option to other tumor types. In addition, we are working to improve the expansion protocols and the specific expansion of tumor-recognizing T cells. Finally, the program will also allow for a direct translation of new genitically-modified T cell therapies into early clincical trials