Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma

Soft-tissue sarcomas (STS) are a heterogeneous group of malignancies characterized by both their relatively low incidence and their poor prognosis, encompassing more than 60 distinct diagnoses. Leiomyosarcoma (LMS), together with liposarcoma, is one of the most frequent sub-types amongst STS and accounts for up to 25% of all newly diagnosed STS \[Guo et al., 2015\].

The absence of definite causative risk factors for LMS, whether genetic, epigenetic or environmental, make this disease particularly difficult to understand and difficult to treat.

Classically, soft-tissue sarcomas (STS) have been treated as a single disease and with LMS as one of the most frequent sub-types the results with conventional therapies have been rather disappointing, especially in the advanced setting. The use of novel therapeutic approach such immunotherapy has also not yielded the same success compared to other tumor entities, whereas the heterogeneity of this malignancy certainly plays a role.

Current immunotherapy trials mostly use monoclonal antibodies to target those molecules or interactions, that essentially "take the brakes off" the immune system. If the underlying immune response however is poor, simply taking the brakes off will be insufficient. In tumors that do not trigger a sufficient immune response, it might be an advantages strategy to try make the tumor a better target and thus trigger a better antitumor immune response.

Strategies that incorporate the tumoricidal properties of gammadelta T cells (γδ T cells) represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB) \[Dieli et al., 2007\]. An evaluation of pooled data from 132 published in vitro experiments shows a consistent improvement in the cytotoxicity of γδ T cells in the presence of antitumor antibodies. Immunotherapy using γδ T cells alone shows promising clinical activity, but there is a strong preclinical rationale for combining this treatment modality with cancer-targeting antibodies to augment its efficacy \[Fisher et al., 2014\].

Dinutuximab beta was designed to bind to neuroblastoma cells and other cancer cells that express the GD2 antigen, such as STS/LMS cells, and it is believed that this binding "labels" the cells an makes them a better target.

In addition, γδ T cells can safely be expanded in-vivo using intravenous zoledronic acid and subcutaneous interleukin-2 (IL-2) in patients with different types of solid tumors \[Dieli et al., 2007; Pressey et al., 2016\].