Periodic Reporting for period 1 - PanCaVax (Personalised Pancreatic Cancer Vaccination Therapy derived from Autologous Tumor Cells and Neoantigens)
Período documentado: 2018-12-01 hasta 2019-05-31
Today a patient diagnosed with pancreas cancer is facing a very poor perspective. Only 25% of the patients will survive the next 12 months, whereas a discouraging 6% is still alive 5 years after diagnosis.
Contrary to other cancers, hardly any progress in therapy options has been made during the last 40 years.
In 2015, there were an estimated 338,000 new cases of pancreatic cancer and 330,000 pancreatic cancer deaths worldwide. It is the only type of cancer with an annual mortality rate so close to its annual incidence rate. This mainly stems from the early development of systemic metastatic cancer and the late diagnosis.
The high medical need for an effective therapy for pancreatic cancer patients is the major driving force for CyTuVax in its PancaVax project. Pancreatic cancer patients have no real treatment options, as the cancer is resistant to current forms of therapy. Chemotherapy (Gemcitabine) provides only 3.9 – 6.1 months extension of survival. A more recent chemotherapy (Folfirinox) slightly improved the median survival rates for patients with metastatic pancreatic cancer. However, it carries severe side effects and is only suitable for patients with a good performance status.
It is CyTuVax’s ambition with PancaVax to substantially extend the life expectancy of patients with pancreatic cancer beyond 2 years and for some patients realize complete cure.
Contrary to other cancers, hardly any progress in therapy options has been made during the last 40 years.
In 2015, there were an estimated 338,000 new cases of pancreatic cancer and 330,000 pancreatic cancer deaths worldwide. It is the only type of cancer with an annual mortality rate so close to its annual incidence rate. This mainly stems from the early development of systemic metastatic cancer and the late diagnosis.
The high medical need for an effective therapy for pancreatic cancer patients is the major driving force for CyTuVax in its PancaVax project. Pancreatic cancer patients have no real treatment options, as the cancer is resistant to current forms of therapy. Chemotherapy (Gemcitabine) provides only 3.9 – 6.1 months extension of survival. A more recent chemotherapy (Folfirinox) slightly improved the median survival rates for patients with metastatic pancreatic cancer. However, it carries severe side effects and is only suitable for patients with a good performance status.
It is CyTuVax’s ambition with PancaVax to substantially extend the life expectancy of patients with pancreatic cancer beyond 2 years and for some patients realize complete cure.
Technical progress and main results achieved during SME Phase 1
1. PanCaVax vaccine adjuvant
• In Q4-2018, the role of single cytokines Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-12 (IL-12) and GM-CSF on the activation of various immune cells (the multi-arm part of the immune system) has been established.
• In Q1-2, 2019, it has been shown that the application of the multi-cytokine adjuvant creates the optimal conditions for powerful and comprehensive cellular anti-tumor immune responses, engaging all cellular arms of the immune system.
2. PanCaVax vaccine target
• in Q1-2 2019, new organoid lines have been established for pancreatic cancer patients from the Department of Surgery MUMC.
• organoid lines CL-17 and CL-19 that have been cultured for DNA isolation and sequencing. These lines have been sequenced to select neo-antigens and to determine the presence of common neo-antigens among patients.
• the inclusion of liposome encapsulated mRNA into a five cytokines vaccine adjuvant protects the mRNA from destruction and leads to translation of the mRNA into the protein antigens and, most probably, to an immune response.
• results showed that RNAses in the inflammatory fluid did not destroy the mRNA. The injection of the multi-cytokine adjuvant created optimal conditions for extracellular translation of mRNA.
1. PanCaVax vaccine adjuvant
• In Q4-2018, the role of single cytokines Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-12 (IL-12) and GM-CSF on the activation of various immune cells (the multi-arm part of the immune system) has been established.
• In Q1-2, 2019, it has been shown that the application of the multi-cytokine adjuvant creates the optimal conditions for powerful and comprehensive cellular anti-tumor immune responses, engaging all cellular arms of the immune system.
2. PanCaVax vaccine target
• in Q1-2 2019, new organoid lines have been established for pancreatic cancer patients from the Department of Surgery MUMC.
• organoid lines CL-17 and CL-19 that have been cultured for DNA isolation and sequencing. These lines have been sequenced to select neo-antigens and to determine the presence of common neo-antigens among patients.
• the inclusion of liposome encapsulated mRNA into a five cytokines vaccine adjuvant protects the mRNA from destruction and leads to translation of the mRNA into the protein antigens and, most probably, to an immune response.
• results showed that RNAses in the inflammatory fluid did not destroy the mRNA. The injection of the multi-cytokine adjuvant created optimal conditions for extracellular translation of mRNA.
The next steps for remaining part of 2019 until 2022 are:
1. the preclinical proof of concept test,
2. the preparation for the GMP production of the adjuvant
3. as well as the preperation of vaccine target,
4. compiling application file for the approval of the clinical study.
The clinical Phase 1-2a trial with 10 patients will cover a period of 2 years, starting late 2020 at the earliest.
Financing - estimated costs:
Preclinical development - €850.000
Phase 1-2a trial - €2.500.000
Funding is aimed for through both venture capital and non-dilutive funds.
1. the preclinical proof of concept test,
2. the preparation for the GMP production of the adjuvant
3. as well as the preperation of vaccine target,
4. compiling application file for the approval of the clinical study.
The clinical Phase 1-2a trial with 10 patients will cover a period of 2 years, starting late 2020 at the earliest.
Financing - estimated costs:
Preclinical development - €850.000
Phase 1-2a trial - €2.500.000
Funding is aimed for through both venture capital and non-dilutive funds.