Researchers develop new kind of immunotherapy to fight HIV

T it is time to take a step forward in the fight against HIV: The international research team led by Prof. Brian Dennison from the University of Bristol and the University Hospital of Eastern Finland now developed a new class of immunotherapy that can overcome the HIV-transmitting defense mechanism in cancer cells. The study is presented at the 67th European Association of Proteopathology Annual Meeting in ECPE.

Immunotherapy is too new to have a name and is regularly used in cancer studies yet it is a discovery worth pursuing. Here we tried to merge two existing treatments into one therapeutic and are showing an evolution in effectiveness and safety. We are inspired by the success of this acell therapy study lead by the University of Bristol says Brian Dennison from Bristols School of Clinical Translational Medicine the Department of Surgery and the Tumor Immunology Immunotherapy Unit Bristol Medical Practice Authority (BSMA) and Paediatric Outcomes Research Institute (PORE).

For HIVAIDS patients immune-cell therapy has proved to be a robust and effective way to suppress the infection. Such treatment means that the HIV infection is no longer able to shoot to the bone and cause immune-mediated destruction. Most HIV patients are treated with antiretroviral drugs for the grace period during the AIDS epidemic. For those who are immune-suppressed regimens of antiretroviral drugs can be very challenging to resist. HIV is thus an ugly but rarely fatal chronic disease. The researchers have developed a way to overcome this problem with a new class of immunotherapy agents.

To understand fully how immune-cell therapy works scientists must go beyond what was previously known. T cells are white cells in the immune system that produce antibodies to kill invading pathogens. When cells recognize an invading pathogen a specific messenger RNA molecule is produced delivering instructions for constructing a receptor that allowed cells to fight infection by the pathogen.

In addition to this new paradigm the T cell therapy integrates non-targets into the T cells to ensure that the immune system can also recognize a therapeutic target. This gives the immune system the opportunity to attack and eliminate the pathogen rather than the individual who is infected. In contrast to classical cellular immune-therapy (Treg) that fights the infection by activating tumour recognition receptors within around the infected cells this T cell therapy addresses both by optimizing the balance between the two cellular signalling pathways that are activated by Treg cells (Treg-1 Treg-2) in order to stop tumor recognition (RTS) and to inhibit uncontrolled growth once the pathogen has been cleared.

We have worked on the Treg-1 molecule and its interaction with RTS. The balance between these two pathways which control the immune response has been shown to be important for tumor recognition by the Treg cell. By enhancing the effectiveness of the Treg-1 and Treg-2 receptors we have been able to overcome the element of chance to develop a new class of therapeutic agents advanced T cells which have exponentially increased antidiabetic efficacy and are very natural to use in HIVAIDS patients explains Dr. Frank Battaglia Boi first author from BIOLODEN of the University of Helsinki Lead author for the PIZZEN study Research Faculty Clinic of Life Sciences University of Helsinki and this is one of the main types of studies translated into a functional mechanism that drives advance in HIV therapeutics.

In addition to the improvement in symptoms by giving patients more time since symptom onset we have also been able to see an absolute improvement in survival as well as in other metabolic conditions such as blood glucose body fat composition cholesterol and blood pressure which are very important for determining survival years after infection.

Immunotherapy has become a promising new class of therapy against HIV. As such there is a great opportunity to define how this therapy will change the rates of HIV invidual and prevention. In our study two HIV patients who are living with chronic viral infections one HIV positive for over 40 years and the other who is a young HIV-positive for only 8-9 months showed a complete reversal of HIV disease progression even in recent years says Brian Dennison.

His study was published in Nature Communications.