3 days popular7 days popular1 month popular3 months popular

HIV immunotherapy shows characteristics considered vital to treating HIV

Pharmaceuticals, Inc. has announced that results from a 12-patient phase I study of ’s immunotherapy, PENNVAX®-B, in -infected patients revealed that immune response characteristics generated by the immunotherapy were similar to those observed in -infected individuals who without treatment do not progress to further stages of the disease.

These extremely rare individuals who self-regulate their are called “long-term non-progressors” and it is believed that part of their ability to control infection may lie in their unique immune responses. In this phase I study, Inovio’s HIV immunotherapy, which had been previously tested only in disease prevention, drove the expansion of activated HIV-specific CD8+ T cells with functional characteristics similar to those of long-term non-progressors.

Results from this clinical study appeared in the peer-reviewed journal Molecular Therapy, in the article, “Synthetic consensus HIV-1 DNA induces potent cellular immune responses and synthesis of granzyme B, perforin in HIV infected individuals,” authored by Inovio researchers and collaborators.

Dr. J. Joseph Kim, President & CEO of Inovio, said, “These results show the ability of our HIV immune therapy to activate HIV-specific CD8+ T cells in infected patients and the potential to go beyond virus control and reach into reservoirs of the infection to halt progression of HIV. Based on these initial results, Inovio plans to conduct a treatment-focused trial with its lead HIV vaccine, PENNVAX®-GP, that broadly targets globally significant HIV strains. This therapeutic study will complement our planned phase I vaccine study of PENNVAX®-GP in healthy subjects.”

HIV targets the immune system, specifically CD4+ T cells, which are responsible for activating CD8+ killer T cells that can kill the virus and infected cells. Unfortunately, with fewer CD4+ and CD8+ T cells, most infected individuals are unable to fight the virus. Independent studies have shown, however, that some untreated have controlled viral replication and are long-term non-progressors (up to 30 years). One reason this may occur is due to the presence of CD8+ T cells with particular functional characteristics. While today’s commonly used antiviral drugs can control viral replication, they cannot eliminate the virus, their long term effect often diminishes, and they have other associated side effects and disadvantages. Immunotherapies capable of generating antigen (disease)-specific CD8+ killer T cells are therefore considered a promising avenue to achieve long term prevention, viral load control, and elimination of HIV.

Inovio’s synthetic immunotherapy technology is very effective at generating disease-specific killer T cells in the body. In this phase I study, HIV-infected individuals whose viral load was already effectively suppressed (below detection level) using a highly active antiviral therapy (HAART) received a four-dose regimen of PENNVAX®-B. Investigators observed that Inovio’s HIV immunotherapy, which in a prior published study in healthy subjects generated best-in-class CD8+ T cell responses, significantly increased antigen-specific CD8+ T-cell responses in all patients.

The investigators also observed that the cell-killing substances granzyme B and perforin (both necessary to kill targeted cells and viruses) produced by activated CD8+ killer T cells were present in quantities and characteristics similar to those of long-term non-progressors. This result mirrors those of the previously published HIV study as well as those of Inovio’s HPV immunotherapy, which also generated best-in-class functional T cells in a phase I study and achieved statistically significant clinical efficacy in a phase II study.

Another striking result of this HIV study was that PENNVAX®-B increased the number of HIV-specific CD8+ killer T cells displaying the receptor integrin, which is associated with the ability to carry T cells to the gastrointestinal tract (GIT). The GIT hosts 40-65% of the body’s total immune cells, hence is the most important target organ for HIV, which targets CD4+ T cells and hides in “gut mucosa.” The increased presence of integrin suggests the potential of such an immunotherapy to better fight or eradicate these reservoirs of HIV infection in the GIT.

The therapy was well-tolerated and did not result in any adverse events.

Source

Synthetic Consensus HIV-1 DNA Induces Potent Cellular Immune Responses and Synthesis of Granzyme B, Perforin in HIV Infected Individuals, Matthew P. Morrow, Pablo Tebas, Jian Yan, Lorenzo Ramirez, Anna Slager, Kim Kraynyak, Malissa Diehl, Divya Shah, Amir Khan, Jessica Lee, Jean Boyer, J. Joseph Kim, Niranjan Y. Sardesai, David B. Weiner and Mark L. Bagarazzi, Molecular Therapy, doi:10.1038/mt.2014.245, published 22 December 2014.

Source: Inovio Pharmaceuticals Inc