In the Journals

All-in-one immunotherapy approach kicks, kills HIV

Robbie B. Mailliard, PhD
Robbie B. Mailliard

Researchers developed an all-in-one immunotherapy that activates cytomegalovirus-specific CD4+ T cells to expose HIV hiding in the immune system and mobilizes HIV-specific CD8+ T cells to eliminate it, according to findings published in EBioMedicine.

The “kick and kill” design uses engineered dendric cells — common in cancer immunotherapy — to activate the cytomegalovirus (CMV)-specific T helper cells, on the thinking that these cells also make up a large part of the latent HIV reservoir.

“Using this dendritic cell-based immunotherapeutic approach, it may be possible to achieve two major goals for the price of one by having the dendritic cells programmed to specifically stimulate both the activation — and therefore exposure — of CMV-specific CD4+ T cells infected with HIV-1 and the activation of HIV-1 specific killer CD8+ T cells that can recognize and eliminate those HIV-1 infected target cells,” Robbie B. Mailliard, PhD, assistant professor of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health, told Infectious Disease News.

Most adults are infected with CMV, including approximately 95% of patients with HIV, Mailliard and colleagues explained. CMV is usually latent, with 25% of T cells in some patients being specific to the virus, according to the researchers.

A major barrier to a functional HIV cure has been finding the cells that harbor latent HIV during ART and exposing them to be eliminated, Mailliard and colleagues noted.

For their study, they collected blood from HIV-1-infected individuals virally suppressed on ART who were enrolled at the Pittsburgh site of the Multicenter AIDS Cohort Study. They isolated dendric cells and engineered what are called antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1). They then tested the cells’ ability to induce HIV-1 latency reversal.

According to the study, not only were the engineered cells able to “kick” HIV out of hiding, they also activated the expansion of HIV-specific CD8+ T cells capable of killing the exposed HIV.

According to a news release, the researchers are pursuing funding for clinical trials to test MDc1 in humans.

“We believe it is indeed a positive step in [the] direction [of a cure], and importantly, we believe that the approach is safe,” Mailliard said. “However, there are still hurdles to be addressed. We hope to learn more as we move toward the clinic with this work.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

Robbie B. Mailliard, PhD
Robbie B. Mailliard

Researchers developed an all-in-one immunotherapy that activates cytomegalovirus-specific CD4+ T cells to expose HIV hiding in the immune system and mobilizes HIV-specific CD8+ T cells to eliminate it, according to findings published in EBioMedicine.

The “kick and kill” design uses engineered dendric cells — common in cancer immunotherapy — to activate the cytomegalovirus (CMV)-specific T helper cells, on the thinking that these cells also make up a large part of the latent HIV reservoir.

“Using this dendritic cell-based immunotherapeutic approach, it may be possible to achieve two major goals for the price of one by having the dendritic cells programmed to specifically stimulate both the activation — and therefore exposure — of CMV-specific CD4+ T cells infected with HIV-1 and the activation of HIV-1 specific killer CD8+ T cells that can recognize and eliminate those HIV-1 infected target cells,” Robbie B. Mailliard, PhD, assistant professor of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health, told Infectious Disease News.

Most adults are infected with CMV, including approximately 95% of patients with HIV, Mailliard and colleagues explained. CMV is usually latent, with 25% of T cells in some patients being specific to the virus, according to the researchers.

A major barrier to a functional HIV cure has been finding the cells that harbor latent HIV during ART and exposing them to be eliminated, Mailliard and colleagues noted.

For their study, they collected blood from HIV-1-infected individuals virally suppressed on ART who were enrolled at the Pittsburgh site of the Multicenter AIDS Cohort Study. They isolated dendric cells and engineered what are called antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1). They then tested the cells’ ability to induce HIV-1 latency reversal.

According to the study, not only were the engineered cells able to “kick” HIV out of hiding, they also activated the expansion of HIV-specific CD8+ T cells capable of killing the exposed HIV.

According to a news release, the researchers are pursuing funding for clinical trials to test MDc1 in humans.

“We believe it is indeed a positive step in [the] direction [of a cure], and importantly, we believe that the approach is safe,” Mailliard said. “However, there are still hurdles to be addressed. We hope to learn more as we move toward the clinic with this work.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.