Immunicum has announced the publication of a scientific abstract that discloses new preclinical data on DCP-001, the company’s lead clinical candidate, in combination with 5’-azacitidine (5-AZA), a hypomethylating agent, and venetoclax (VEN), a BCL2 inhibitor, in a preclinical setting.
The in vivo and in vitro data support the evaluation of DCP-001 as a potential combination therapy with 5-AZA+VEN in acute myeloid leukemia (AML) and related hematological malignancies and demonstrated stronger tumor volume reduction in combination than either vaccination or drug treatment alone.
“The preclinical data that will be presented at the upcoming CIMT meeting provides a promising snapshot of the therapeutic potential of combining relapse vaccination using DCP-001 with a highly active treatment regimen especially for elderly AML patients. The use of DCP-001 in this setting could broaden the positioning of DCP-001 beyond the AML maintenance setting with a focus on supporting patients reaching complete response,” says Alex Karlsson-Parra, Chief Scientific Officer at Immunicum. “We expect to further build upon this preclinical data with updated clinical data from the ADVANCE II study in the near term, which evaluates DCP-001 as monotherapy in the AML maintenance setting. Together, these data sets will add to the growing body of data to further validate this program and its potential for the treatment of AML.”
DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of Immunicum’s human DCOne myeloid leukemic cell line into a mature dendritic cell phenotype. This results in a vaccine comprising a broad array of endogenous tumor-associated antigens combined with a mature dendritic cell costimulatory profile. Preclinical studies suggest that upon intradermal vaccination, DCP-001 is phagocytosed by local and recruited antigen-presenting cells (APC), resulting their activation and migration to the draining lymph nodes to (re)activate tumor-reactive T-cells. In clinical studies, intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in AML. Importantly, immunomonitoring confirmed that DCP-001 vaccination resulted in anti-tumor immune responses that correlated with long-term survival.
To evaluate a potential combination of DCP-001 vaccination with 5-AZA + VEN in a preclinical setting, a humanized mouse model for AML was used. Mice were randomized and assigned to four groups: untreated control, vaccination alone, treatment with 5-AZA + VEN alone, and combination. The mean tumor volume 6 weeks after therapy initiation was significantly reduced in the combination group (181.8 ± 29 mm3) as compared to control (522 ± 97.5 mm3), but also vaccination (326.9 ± 54.6 mm3) or drug treatment alone (293.8 ± 29 mm3). Additional in vitro studies detected no negative impact of 5-AZA + VEN on the viability, recovery or phenotype of DCP-001. Moreover, no influence of either 5-AZA or VEN was observed on the ability of DCP-001 to stimulate proliferation of allogeneic peripheral blood lymphocytes or on the ability of allogeneic monocyte-derived immature dendritic cells to endocytose DCP-001-derived cellular content, a key component of the mechanism-of-action.
Photo of Alex Karlsson Parra: Immunicum