UB, the first centre in Spain accredited for the development of advanced therapy medicinal products with HIV

Researchers Josep M. Canals, Jordi Alberch and Felipe García.
Researchers Josep M. Canals, Jordi Alberch and Felipe García.
Research
(14/04/2015)

The Spanish Agency of Medicines and Medical Devices (AEMPS) has accredited the University of Barcelona (UB) for the development of advanced therapy medicinal products (ATMPs) with the human immunodeficiency virus (HIV) at the clean room of the Research and Development Unit, included in the Cell Therapy Program of the University of Barcelona (TCUB).

The first medicinal product that the Unit will produce is the cell HIV vaccine which will be used on a clinical trial led by the Hospital Clínic de Barcelona.

Researchers Josep M. Canals, Jordi Alberch and Felipe García.
Researchers Josep M. Canals, Jordi Alberch and Felipe García.
Research
14/04/2015

The Spanish Agency of Medicines and Medical Devices (AEMPS) has accredited the University of Barcelona (UB) for the development of advanced therapy medicinal products (ATMPs) with the human immunodeficiency virus (HIV) at the clean room of the Research and Development Unit, included in the Cell Therapy Program of the University of Barcelona (TCUB).

The first medicinal product that the Unit will produce is the cell HIV vaccine which will be used on a clinical trial led by the Hospital Clínic de Barcelona.

 
Pioneering facilities

The clean room of TCUBʼs Research and Development Unit, led by Josep M. Canals, researcher in the Faculty of Medicine of the University of Barcelona (UB) and the research institute IDIBAPS, has gone through a two-year process to comply with AEMPSʼs correct manufacturing regulation.

According to Canals, “the accreditation to produce a cell therapy medicinal product with HIV in the clean room of the Unit is the step needed to make the switch from basic research to clinical research”. “Moreover —he adds—, it provides researchers, research centres and companies with opportunities to develop here the whole process to produce other ATMPs, including gene therapy and regenerative medicine”.

The vice-rector for Research, Innovation and Transfer of the UB, Jordi Alberch, emphasizes that “the commitment to university-hospital collaboration will improve campusʼ research activity in advanced new therapies and translational medicine”.

Advanced therapies are new medical products for human use based on cells (cell therapy), genes (gene therapy) or tissues (tissue engineering). Spain, with about fifty medical products in phase of clinical development, is a leading country in the field of ATMPs. There are about fifteen cell production rooms, but most of them only serve the hospitals and research centres that host them and they are not accredited to produce viruses. Therefore, the development of gene therapy products for clinical trials happens outside the country.

The accreditation allows TCUBʼs Unit performing all the phases of the process to produce the cell vaccine to treat AIDS in a new phase II clinical trial that will be developed by the research team led by Dr Felipe García, senior consultant at the Service of Infectious Diseases of the Hospital Clínic de Barcelona. “Advanced therapies, particularly gene therapy and therapeutic vaccines, like the ones that will be used in the clinical trial are the focus of new experimental strategies that aim at developing a functional cure of HIV infection”, says García.

In order to get the accreditation, UB and Hospital Cliníc research groups have worked cooperatively and repeated the process to product the cell vaccine up to six times: from the moment in which cell source is obtained to the moment it gets into facilities, it is processed and the final product is obtained. This long process ensures maximum quality and security to patients who will receive the medical product, which requires extremely complex procedures.

The procedure to develop the vaccine requires working in very specific facilities with high level standards of security that enable to move patientʼs virus into the lab, a crucial step for the development of the vaccine. TCUBʼs facilities are the only ones which allow performing the procedure in Catalonia and the only accredited centre in Spain.

 

Production of the cell vaccine

The beginning of the cell vaccine production is imminent ant it will last until well into 2017. The process lasts about a year; it includes the isolation and purification of the autologous virus. Then, in a second sample, patientʼs dendritic cells (DC) are isolated and exposed to patientʼs own virus, which is previously isolated, expanded and inactivated at the facilities of the Unit.

DCs play a critical role in the presentation of antigens to T lymphocytes and the regulation of bodyʼs immune response. During the process of production, DCs are exposed to inactive autologous HIV. These cells phagocyte the virus and break it into small fragments; some of these fragments adhere DC membrane. When they are mature, DCs —also named pulsed cells— are the cell vaccine that will be administered to the patient. The objective is to get that patientʼs immune system responds against the virus, so it will not be necessary to maintain the combination antiretroviral therapy (cART) throughout patientʼs entire life.

The virological response results obtained on a previous trial, —described on a study led by Dr Felipe García published in 2013— are the best ones shown by a therapeutic vaccine. In the study, most vaccine recipients were able to temporarily control viral replication with a peak reduction above viral load set point of 93%. This figure is similar to the response to antiretroviral medications when they are used as monotherapy with antiretroviral drugs. This trial has been the strongest proof of concept in the scientific literature that a therapeutic vaccine is feasible.

 

The Research and Development Unit of TCUB

The Research and Development Unit of TCUB, located on a 300m2 area at the Faculty of Medicine of the UB, has two cell culture rooms and a laboratory to carry out preclinical research with human cells, including rooms for pluripotent stem cells, such as embryonic ones. The facility also includes three GMP (good manufacturing practices) cell production rooms.

Moreover, the facility has the first gene and cell therapy lab in Catalonia. The unit is composed by four qualified technicians who give advice to develop and apply new advanced therapy medical products.
In the future, it is planned that the UB room will host the production of an intermediate product to perform a clinical study focused on cell immunotherapy based on T lymphocytes with chimeric antigen receptor (CAR) in patients with chronic lymphocytic leukemia (CLL) and acute lymphoid leukaemia (ALL), promoted by the services of Immunology and Hematology of the Hospital Clínic. Together with the Institute for Bioengineering of Catalonia, some tissue engineering strategies to produce 3D tissues and organs in GMP facilities are also being developed.