OvaCure Research 

 

Each of OvaCure’s projects is conducted by world-leading experts within the fields of immunotherapy, oncology and gynaecology and is guided by OvaCure’s Scientific and Clinical Advisory Board. 

Only ground-breaking projects are selected
In collaboration with the Anticancer Fund and the OvaCure Scientific and the Clinical Advisory Board, OvaCure has generated a project portfolio of two Danish and three international projects. Each project developed through OvaCure has maximum potential for the development of curative treatments for ovarian cancer patients.

OvaCure's first five projects are currently underway, with the flagship project, T-cell Infusion, being among the world's first trials to treat ovarian cancer patients with adoptive T-cell therapy (ACT). OvaCure’s 2nd project, T-cell Combination, will be conducted under the same clinical trial protocol and further the investigation by combining ACT with IFNα and chemotherapy. These two projects are the result of the OvaCure Innovation Summit in 2014, and have inspired the development of two additional international projects in Lausanne, which aim to develop novel personalised vaccination programs for ovarian cancer patients. OvaCure's Innovation Summits and Collaboration Labs in 2016 have also initiated, co-created and developed two additional projects, Genetic-Match and CAR T-cell Project, which are planned to start December 2016.

 
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Initiated Projects

T-cell Infusion Project (Denmark)

Original title: “Immunotherapy by adoptive T-cell infusion in the event of advanced ovarian cancer (stage III and IV) and treatment trials for a total of 18 women”.

The project is conducted at the Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital Herlev, Copenhagen, Denmark. Principal investigator: Head of OvaCure Immunotherapy Dream Collaboration, Professor Inge Marie Svane, MD, PhD. 

  • Ovarian cancer patients in this trial are among the first in the world to be treated with T-cells 26 relapsed ovarian cancer patients will be treated in total
  • Centre for Cancer Immune Therapy in Copenhagen is a world leader in T-cell therapy
  • 55% success rate in melanoma with this method already Proven Project lead, Prof. Inge Marie Svane is a pioneer in Adoptive T-cell therapy

T-cell Combination Therapy Project (The Netherlands)

Original title: “Combined chemo and adoptive T-cell therapy (ACT) as treatment for recurrent epithelial ovarian carcinoma”.

This project is conducted at the Leiden University Medical Center, Leiden, the Netherlands. Principal investigator: Els M. E. Verdegaal, PhD. 

  • 18 ovarian cancer patients to be treated by Q4 of 2017
  • Aims to provide a lower toxicity treatment regimen
  • Stands to improve T-cell function after re-infusion using chemotherapy and Interferon alpha
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Personal T-Cell Project (Switzerland)

Original title: “Harnessing tumour diversity to develop personalised adoptive immunotherapy for ovarian cancer”.

This pre-clinical project is conducted at the Ludwig Center for Cancer Research, University of Lausanne, Switzerland. Principal investigator: Professor George Coukos, MD, PhD. 

  • Harnessing the diversity and micro-environment of the patients’ tumour
  • Establishing robust pre-clinical methods for application in a clinical setting

Personal Vaccine Project (Switzerland)

Original title:  "A Phase I/II study to test the feasibility, safety and immunogenicity of personalised mutanome peptide (PMP) vaccine vs. whole tumour oxidized lysate (OC-L) vaccine admixed with CpG adjuvant, in combination with low-dose cyclophosphamide in primary advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer".

This clinical project is conducted at the Ludwig Center for Cancer Research, University of Lausanne, Switzerland. Principal investigator: Professor Lana Kandalaft, MD, PhD. 

Making immunotherapy even more personal for ovarian cancer

  • 20 ovarian cancer patients will be administered with two different vaccines starting in Q4 2016
  • Project goal is to develop the best vaccine approach as a primary treatment for ovarian cancer
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Tumour-Match Project (Denmark)

Original title: ”Molecular profiling of advanced gynaecological cancers in targeted therapies”.

This project will be conducted at Nordic Society of Gyneacological Oncology at Rigshospitalet, Denmark. Principal investigator: Mirza, Mansoor Raza, MD, Chief Oncologist.

  • A retrospectivecancer study
  • Started December 2016
  • Project identifies patients who respond to different combinations of cancer treatments and uses this to improve clinical trials and treatments
  • Economic and health benefits of treatment that is matched to a patient’s genetic profile


OvaCure Pipeline

CAR T-cell Therapy Project (USA)

Original title: State-of-the-art CAR T technology applied to ovarian cancer patients for the first time”.

This project will be conducted at the Perelman School of Medicine, the University of Pennsylvania, PA, USA. Principal investigator: Professor Daniel Powell, MD

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Immunotherapy

The human immune system
In brief, the human immune system is the body’s defence mechanism against invasion of foreign elements. These elements are most often microorganisms that cause infectious diseases. The immune system consists of various different cells, antibodies, cell receptors and signalling molecules. The immune system is arranged and coordinated by a complex system of regulatory mechanisms that may accelerate or stop certain proceedings in order to achieve the desired immune response. Thus, there are several pathways in which the immune system can be stimulated in many different directions.

Recently, the role of the immune system in cancer diseases has been firmly investigated. There are now several different types of cancer treatments that involve manipulation of the immune system. Usually, these treatments are categorized as immunotherapy.

The treatment principle of immunotherapy is that it modulates the patient’s own immune system, which causes the body to eliminate the malignant cells. Several immunological treatments are currently being developed. Some of these are immunomodulation agents that may accelerate or block certain immunological pathways in order to produce the desired anti-cancer response. These will typically have a general effect on the immune system and can be produced and administered to many patients with the same type of cancer disease.  

Adoptive cell transfer immunotherapy
Another type of immunotherapy treatment is based on infusions of very specifically and highly active immunological cells. In brief, these are tailor-made to target the genetic fingerprint of one specific tumour. The latter category includes Adoptive Cell Transfer Immunotherapy (ACT) with tumour-infiltrating lymphocytes (TILs). In brief, immunological “killer cells” (the tumour infiltrating lymphocytes) are harvested from the patients’ individual tumour and afterwards amplified in a laboratory under optimal conditions. Following, the cells are transfused back into the patient where the now abundant cells recognise and destroy tumour cells. Most often the treatment will be combined with immunomodulation agents in order to achieve a more effective immunological response. Each treatment is thereby made uniquely to the individual patients’ tumor.  

Treatment with ACT has shown an effect in 40% of patients with melanoma, which is remarkable for this patient category. Pre-clinical data suggest that ovarian cancer tissue contains TILs that can be harvested. Consequently, treatment with ACT could be developed for ovarian cancer patients. A small trial from Japan examined the use of TILs as maintenance therapy in ovarian cancer and found that 100% of the patients treated with TILs were disease-free compared to 68% of the patients in the control group. These encouraging results indicate that treatment with TILs may potentially cure ovarian cancer.  


The main difference between immunotherapy and traditional antineoplastic treatments

In contrast, immunotherapy activates the body’s own immune cells to kill the cancer cells. As a result, treatment with immunotherapy does not have the same harmful effects as chemo- and radiotherapy and is therefore much better tolerated by patients.

 

Traditional chemotherapy and radiotherapy works by directly killing or inhibiting the growth of the malignant cells. However, both chemotherapy and radiotherapy affects not only the malignant cells but also the healthy normal-functioning cells. This leads to the well-known toxic side-effects such as nausea, vomiting, headaches, muscle pain, hair loss and fatigue, which can impact the fragile cancer patients quite severely. 


What is Ovarian Cancer?

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Ovarian cancer is characterised by the presence of cancerous or malignant cells in the ovaries. These cells then form a tumor which can be identified based on their origin. There are 3 main types of ovarian cancer tumors:

Epithelial tumors: These tumors originate from cells which cover the outer surface of the ovary. Most ovarian tumors are epithelial cell tumors.

Germ cell tumors: These originate from the cells that produce the reproductive eggs or ova.

Stromal tumors: These originate from cells which provide the structural support for the ovaries and produce the female hormones estrogen and progesterone.

 

 

Symptoms
The symptoms of ovarian cancer are often uncharacteristic, vague and/or slowly emerging. The symptoms may consist of the sensation of a pelvic or abdominal mass, pain in the pelvis or abdomen, an altered sensation or pattern of toilet habits or obstipation, nausea, vomiting, dyspnoea and/or fatigue.

Prevalence
There is an estimated 239,000 new cases worldwide each year. A total of 140.000 women worldwide die annually from ovarian cancer including more than 400 Danish, 1.700 Nordic and 45,000 European women.

 

Incidence
Denmark has one of the highest incidences of ovarian cancer in the world. The lifetime risk of developing ovarian cancer being about 2% for Danish women compared to 1.4% - 1.8% in the United States (Reference: Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature Digant Gupta and Christopher G Lis, Journal of Ovarian Cancer Research).

Diagnosis
When the patient is referred with symptoms suspected of ovarian cancer, a combined gynaecological and ultrasound examination is conducted. A cancer biomarker (CA125) is obtained from a blood sample. If patient's are suspected of having ovarian cancer, additional imaging modalities such as MRI, CT or PET/CT may be used prior to surgery or biopsy. The diagnosis can only be truly confirmed by histological examination from a biopsy or from removal of tumor masses. So far, there is no method for screening for ovarian cancer.

Survival
Survival of ovarian cancer is highly correlated to the stage of disease at the time of diagnosis. In Denmark, the 5-year overall survival for women with ovarian cancer in stage I, II, III and IV are 83%, 62%, 23% and 14% respectively. Unfortunately, the vast majority of women are diagnosed in stage III and IV.