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Prostate Cancer Therapy Research Group

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Back row from left to right: Yaping Hua, Kristina Førde, Benjamin Gabriel, Karl-Henning Kalland, Seyed Mohammed Lellahi, Hua My Hoang. Front row: Rebecca Nguyen, Waqas Azeem, Minh Thu Le, Anne Margrete Øyan

The Prostate Cancer Therapy Research Group is headed by: 

Professor Karl-Henning Kalland and has long experience in advanced molecular studies of gene expression regulation in normal cells, virus-infected cells and cancer cells

The group is an authorized Research Group of the Norwegian Cancer Society

Group leader Karl-Henning Kalland is Principal Investigator of Centre of Excellence CCBIO:

 

Centre for Cancer Biomarkers CCBIO | University of Bergen (uib.no)

 

Dendritic cell-based therapy:

The treatment is called cryoimmunotherapy (CryoIT) and has been tested in the first Phase I clinical trial at Department of Urology, Haukeland University Hospital. 18 patients with metastatic and castration-resistant prostate cancer were treated with good safety and encouraging efficacy data during follow-up.

A revised CryoIT protocol will be used for the next stage clinical trial in preparation. Robust production of more potent dendritic cells and new biomarker development is important for the upcoming clinical trial.

Drug discovery and development:

Currently the IL6/STAT3 and WNT/b-catenin pathways, and IDO-1 regulation are focused.  Both FDA-approved drug panels and novel phytochemically isolated drug panels have been screened. Several patent applications and publications have resulted from this approach.

Collaborators for Cryoimmunotherapy:  

Clinical Research Post - Bjørn Tore Gjertsen, Medical advisor

Urology - Christian Beisland, Principal Investigator; Alfred Honoré

Oncology - Svein Inge Helle; Oddbjørn Straume

Gynecology - Line Bjørge

Radiology - Lars Anders Rokne Reisæter; Martin Biermann

Pathology - Lars Andreas Akslen

Microbiology - Elling Ulvestad

Immunology and transfusion medicine - Einar K. Kristoffersen; Guro Melve; Kimberley Hatfield

Radium Hospital, Department of Cell Therapy, Oslo - Gunnar Kvalheim

Liquid biopsies: Klaus Pantel - University Medical Center Hamburg-Eppendorf (UKE)

Molecular analyses: Ian G. Mills - Queen’s University of Belfast & University of Cambridge

Collaborators for Drug Discovery and Development:

Professors Weidong Zhang, Xisong Ke, Yunheng Shen, Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai.

The research has received support from Einar Galtung Døsvig, Espen Galtung Døsvig, Jan Einar Greve, Thorstein Selvik, Kåre Rommetveit, Trond Mohn, Herman Friele, Bjarne Rieber, Tordis and Fritz C. Rieber’s legacy, the Research Council of Norway (programs NFR BEHANDLING; Centre for Cancer Biomarkers (CCBIO)) and the Norwegian Cancer Society.

Status of the cancer immunotherapy:

Immunotherapy has revolutionized cancer therapy during the last 15 years. Still, the 2 most successful types, immune checkpoint inhibition and CAR T-cell therapy, are curative only in selected cancer types and even so in less than 50 % of patients with advanced cancer. Dendritic cell (DC)-based cancer therapy has been tested altogether in several hundred clinical trials. The current overall conclusion is that safety and patient tolerability have been satisfactory, but therapeutic effects have not met the high hopes and expectations. We now understand several reasons why the full potential of DC-based immunotherapy has not been realized. One reason is that DCs commonly have been “trained” to attack only one single tumor-associated antigen, thus not taking cancer heterogeneity into account. Our CryoIT approach tackles this problem by placing immature DCs in the inflammatory cryoablated cancer tissue so that the DCs may detect and process the entire collection of tumor-associated antigens that exist in each tumor. Our work has identified additional challenges. Textbooks and a large part of the published literature present a dichotomous view of DC differentiation according to which DCs become either tolerogenic or pro-inflammatory. We have found that, at least in cell culture, all tested maturation protocols lead to DCs expressing both tolerogenic and pro-inflammatory features simultaneously. Better insights and control of molecular pathways that become activated during DC differentiation could generate more potent pro-inflammatory DCs. Additionally, it is well documented that physiological negative feedback mechanisms are at play in the body to limit immune attacks. DC viability and longevity represent additional challenges that we recently have become aware of. Optimal control of such normal processes might be necessary to make DC-based cancer therapy efficient enough to treat cancer. More molecular and cellular network insights are required to take out the full potential of DC-based therapy. Our group additionally works on biomarkers in order to obtain more precise results of clinical trials, including ultradeep T-cell receptor sequencing and an In vivo-mimicking Ex vivo-model of standardized tissue explants.

RESEARCH | MEDICINE

Current challenges

The main challenges will be: 1) Establish Good Manufacturing Practice (GMP)-grade production av therapeutic dendritic cells in Bergen for the CryoIT next phase clinical trial; 2) Revision of the CryoIT protocol and planning and funding of next phase clinical trial; 3) Establish a new In vivo-mimicking Ex vivo-model of patient materials for new quality control tests of therapeutic cells and drug combinations.

 

 

 

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