Cancer Cells and Reprogramming Plasticity

Research focus

The main priority of the Kalland group is dendritic cell-based cryoimmunotherapy (CryoIT) as a new cancer treatment modality, including integrated drug discovery and biomarker development.

Subprojects

1. CryoIT: Having completed the phase I clinical trial for metastatic prostate cancer, the group now prepares for the next phase clinical trial. The main efforts in 2022 and forwards are directed towards robust production of potent therapeutic dendritic cells (DCs) in Bergen.

2. Drug Discovery and Biomarker Development: The screening part of this project has utilized both a panel of phytochemicals available in collaboration with Shanghai and a panel of drugs approved for treatment of human and animal diseases according to the repurposing strategy. Currently, the transcription factors STAT3, androgen receptor (AR), b-catenin and inhibitors of the enzyme Indoleamine 2,3-dioxygenase 1 (IDO1) are investigated.

Important results

CryoIT: Good manufacturing practice (GMP) grade DCs and standard operating procedures are currently established using the Miltenyi CliniMACS Prodigy closed system. The DC product is compared to manually produced monocyte derived DCs and conventional type 1 (cDC1) and type 2 (cDC2) that circulate in normal blood. Results that may be very important include the observations that when immature DCs mature in vitro according to widely used routine conditions, then pro-inflammatory and tolerogenic features co-develop. Additionally, in vitro viability of DCs is compromised due to spontaneous apoptosis induction. Molecular and cellular control of such features could generate more potent therapeutic immune cells.

The European Patent Office has approved the patent application of CryoIT combined with intra-tumoral injection of an immune checkpoint inhibitor. The national implementation phase is ongoing.

Drug Discovery and Biomarker Development: The group’s repurposing strategy has previously published two compounds that inhibit β-catenin signaling in cancer cell lines, and the molecular targets and mechanisms were identified. Novel compounds with STAT3-inhibiting activity have been discovered, and one of the compounds exhibited dual inhibition of both androgen receptor (AR) and STAT3. Patent applications have been submitted. In parallel, relevant biomarkers are explored, e.g., T-cell receptor sequencing.

Future plans

The overarching focus and aim will be to develop enhanced immunotherapy against cancer. Kalland envisages a next stage clinical BASKET trial during 2023-2025 and a next generation CryoIT protocol thereafter. The BASKET trial will include patients with prostate cancer, kidney cancer and vulvar cancer. The next generation CryoIT protocol will be enhanced by more robust and potent therapeutic dendritic cells. Biomarker development and implementation in the next clinical trial includes T-cell receptor sequencing and in vivo-mimicking ex vivo culture models to assess lymphocyte and dendritic cell functionalities.

PubMed Publications

Find Kalland's PubMed publication list here.