The Wistar Institute has secured a landmark $17 million, five-year grant from the National Institutes of Health to launch the iCure Consortium, an ambitious initiative aimed at developing personalized HIV cure strategies. The Philadelphia-led consortium represents the first comprehensive effort to tailor HIV eradication therapies to individual patients' unique viral characteristics.
"Today 38 million people still live with HIV worldwide, and 1.3 million contract the virus each year," said Luis J. Montaner, D.V.M., D.Phil., iCure principal investigator, executive vice president of The Wistar Institute and director of Wistar's HIV Cure and Viral Diseases Center. "For the first time, this grant brings our best team together working towards a cure tailored to each participant by pairing the latest in neutralizing antibody and cell-therapy breakthroughs against the unique, person-specific features of HIV."
Six-Component Personalized Therapy Strategy
The iCure Consortium will test a comprehensive six-part, individually-tailored therapy designed to eliminate the persistent viral reservoir that remains after antiretroviral therapy. The innovative approach combines neutralizing antibodies, mRNA therapy, viral binders, engineered CAR-T and "Natural Killer" (NK) cells, and precision latency "wake-up" drugs—all customized against each patient's unique virus.
"Ending HIV demands more than management—it demands eradication," said Drew Weissman, M.D., Ph.D., iCure co-principal investigator, 2023 Nobel Laureate and Roberts Family Professor in Vaccine Research at the Perelman School of Medicine at the University of Pennsylvania. "This project now allows us to apply our breakthroughs in RNA therapy as part of a cure-directed strategy."
Multi-Step Therapeutic Approach
The iCure strategy operates through a systematic four-step process:
- Wake the latent virus: Researchers reactivate dormant HIV in blood samples to identify viral mutations
- Map and target unique weak spots with tailored antibodies: Development of personalized antibody cocktails against specific mutations
- Destroy infected cells using "super-charged" CAR-T and NK cells: Genetic modification of immune cells to enhance virus-killing capabilities
- Enhance clearance and block relapse with bispecific binders: Deployment of targeting molecules that guide immune cells to infected cells
In the initial phase, researchers reactivate the virus in participant blood samples and identify mutations against which the participant has not yet developed antibodies. They then create tailored antibody therapy cocktails specifically designed against these mutations.
The subsequent stage focuses on preventing HIV recurrence through person-specific antibodies or small molecule binders that function as "homing devices"—beacons that guide immune cells to latent virus locations. Researchers genetically modify CAR-T cells and NK cells to express these targeting mechanisms for enhanced infected cell clearance.
Enhanced NK Cell Technology
The final component involves supercharging NK cells through the development of adaptive NK cells with enhanced virus-killing capabilities. The approach incorporates small-molecule drugs called bispecifics, which bind NK cells directly to their targeted infected cells.
"iCure takes full advantage of the advances made in understanding how and where HIV hides from the immune system," said Montaner. "We've built on our knowledge and can use that information to identify a first of its kind targeting to a person's unique HIV features."
Research Consortium and Future Outlook
The initiative builds upon research groundwork established by the BEAT-HIV Martin Delaney Collaboratory, a Philadelphia-based consortium of more than 95 leading HIV researchers co-led by Dr. Montaner. Participating institutions include Johns Hopkins Medicine, the University of Pennsylvania, Philadelphia FIGHT, the Ragon Institute at Harvard University, George Washington University, Duke University, and Massachusetts Institute of Technology.
Montaner described the NIH grant as a "once in a lifetime opportunity" that reflects Wistar's scientific leadership in HIV cure development and its collaborative relationship with the HIV community.
"By the end of this study we hope to have a process by which to identify the virus that we need to go after in each person and have a basis to design clinical trials choosing the best of these strategies to move forward," said Montaner.
The iCure program is funded by the National Institute of Allergy and Infectious Diseases, part of NIH, under award number UM1AI191272.
