Cancer Research - Europa

Dendritophages
Therapeutic cancer vaccines
Summary
The patient’s blood monocytes are transformed into eff ector
monocyte-derived dendritic cells (DC) (dendritophages),
which fi ght the patient’s own disease. The therapeutic cell
drug comprises dendritic cells, which are loaded with cancer-specifi
c antigens to activate the patient’s immune
system after re-injection.
This project aims to demonstrate the immune and clinical
effi cacy, reproducibility and feasibility of anticancer cell vaccine
by choosing the best dendritic cell vaccination strategy
via adequate pre-clinical studies (DC diff erentiation and
maturation, tumour antigens selection and loading, dose
delivered, site and vaccination schedule). It will monitor the
immune response in correlation to the clinical response after
defi ning the most relevant immuno-monitoring techniques,
and will demonstrate the immunological effi cacy of DC
immunotherapy in prostate cancer, which will be performed
after loading ex vivo dendritic cells with proteic antigen.
This will require the setting up of quality control criteria and
data base design for the production of the cellular product,
and optimising a GMP process. We will start a clinical trial to
evaluate the cell drug on progressing prostate cancer
patients.
Problem
• Select the most eff ective DC preparation.
• Develop GMP process.
• Show immunogenicity and safety in carcinoma patients.
Aim
Keywords | Vaccine dendritic cells |
The fi nal goal of anticancer therapeutic vaccines is to prevent
metastasis development as well as tumour progression and to
provide long-term protection.
Previous and ongoing clinical studies have shown that there
are no side eff ects associated with this type of dendritic autologous
cellular drugs, and that immune and clinical responses
can be achieved in some patients resistant to conventional
therapies. The preclinical data generated on dendritic cells, as
well as pilot clinical trial data, have driven the dendritic cell
immunotherapy technology to reach adequate maturity to
enter real standardisation and demonstration of immune effi -
cacy. A phase I study of anti-tumour immunisation of patients
with melanoma stage III or IV has been initiated during a previous
EU Project coordinated by the same team, with
autologous DCs (BIO-CT97- 2216, CELLULAR VACCINES,
1997). Nine patients had completed the treatment which consisted
of four series of injections of dendritic cells pulsed with
tumour cell lysate and dendritic cells pulsed with HbsAg and
TetanusT.
Expected results
Results showed excellent safety and the presence of
immune responses after vaccination, as well as signs of clinical
responses in some of the patients. It is to be noted that
one patient showed complete regression of metastases
four months after the last vaccination, and another one
showed stabilisation of the disease.
We have compared several technologies for obtaining DCs
and selected the most appropriate for GMP development.
The initial clinical results have been confi rmed on a randomised
clinical study conducted in malignant melanoma
stage IV patients immunised with dendritic cells pulsed ex
vivo with three melanoma cell lines lysates. The results of
this study are based on 49 treated patients, with 15 patients
having completed the cycle of six DC vaccinations, the others
progressing due to late stage disease. No severe adverse
event has been related to the therapeutic protocol nor to
the DC product; the most frequent minor side eff ects were
injection site reactions. Fourteen patients out of 49 initiated
T-cell immune response against the antigens presented and
ten patients had disease stabilisation; most of these immune
responses and stabilisations were in the group of patients
having received six vaccinations.
Studies are ongoing in colorectal and prostate cancer.
Potential applications
Vaccine therapy of metastatic carcinoma.
186 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME