Novel Anti-HIV CAR-T Cell Therapy Shows Promise for Durable Viral Control in Early Clinical Trial
核心洞察
Caring Cross (搜索)'s first-in-human Phase I/IIa trial of anti-HIV (搜索) duoCAR-T (搜索) cell therapy demonstrated sustained viral control in two participants for nearly one and two years respectively after stopping antiretroviral therapy (搜索).
The therapy showed particular promise in patients who initiated HIV (搜索) treatment early in their infection, with no serious adverse events attributed to the CAR-T cell product itself.
Nine participants received the single-dose treatment using their own genetically engineered T cells (搜索), with conditioning regimens proving crucial for therapeutic efficacy.
Caring Cross (搜索) announced promising early clinical data from a first-in-human Phase I/IIa trial evaluating a novel anti-HIV (搜索) CAR-T cell therapy that demonstrated sustained viral control in select participants. The findings, presented at the American Society of Gene and Cell Therapy Annual Meeting in Boston, suggest the potential for durable immune-mediated HIV suppression without continuous antiretroviral therapy (搜索).
Clinical Trial Design and Participants
The dose-escalation study evaluated the safety and preliminary efficacy of an anti-HIV (搜索) duoCAR-T (搜索) therapy in nine ART-suppressed individuals. The treatment uses participants' own T cells (搜索), which are genetically engineered using Caring Cross (搜索)'s proprietary duoCAR technology before reinfusion.
The study included three distinct cohorts with varying treatment approaches. Cohort 1 received no conditioning regimen, while Cohorts 2 and 3 received mild, non-myeloablative conditioning followed three days later by low-dose or high-dose cell infusions, respectively.
Sustained Viral Control Achieved
Among the six participants in Cohorts 2 and 3, two individuals maintained undetectable to very low viral loads after stopping antiretroviral therapy (搜索) - one for nearly a year and another for nearly two years. A third participant achieved transient control for nearly three months.
"Although the primary focus of the study was safety, a few participants experienced better-than-expected outcomes following interruption of antiretroviral therapy (搜索). We are particularly interested in two individuals who have maintained control of HIV (搜索) with undetectable viral loads for extended periods," said Dr. Steven Deeks, Professor of Medicine at UCSF and principal investigator.
Dr. Mehrdad Abedi, Professor of Medicine and Director of the Alpha Stem Cell Clinic at UC Davis (搜索), noted the significance of the consecutive responses: "While this level of viral control can rarely occur in the absence of intervention, the depth of viral suppression observed after our clinical trial in two consecutive patients in the conditioning arm is especially compelling."
Early Treatment Initiation Key Factor
All three participants who achieved sustained or transient viral control had initiated antiretroviral drugs early in the course of their infection. This timing appears crucial for therapeutic success, as early ART initiation may limit the size and distribution of the viral reservoir, potentially enabling more effective CAR-T cell-mediated control.
Several participants who did not achieve sustained control still demonstrated delayed viral rebound compared to typical kinetics, suggesting some degree of immune-mediated suppression even in partial responders.
Safety Profile
The therapy demonstrated a favorable safety profile, with no serious adverse events attributed to the duoCAR-T (搜索) cell product itself. One participant experienced a drop in blood counts related to the bone marrow conditioning regimen, but this was manageable and expected.
In Cohort 1, where no conditioning was used, no detectable CAR-T cells (搜索) were found in the blood after infusion, and all three participants experienced rapid viral rebound after stopping antiretroviral drugs, highlighting the importance of conditioning regimens for therapeutic efficacy.
Addressing Global HIV Burden
The research addresses a critical unmet medical need, as HIV (搜索) continues to affect approximately 37 million people globally. Despite antiretroviral therapy (搜索) transforming HIV into a manageable chronic condition, it requires lifelong treatment and faces challenges including an estimated 1.3 million new infections annually and more than 700,000 HIV-related deaths each year.
"This work represents the culmination of years of scientific and clinical effort to develop a therapy that harnesses the body's own immune cells to fight HIV (搜索)," said Dr. Boro Dropulić, Founder and Executive Director of Caring Cross (搜索). "While the clinical data are encouraging, the vector used to generate the anti-HIV duoCAR-T (搜索) cells reflects a first-generation design — an important step toward a definitive therapeutic solution."
Future Development
The trial continues with plans to explore modifications such as adjusting the timing of ART interruption or administering multiple infusions to improve outcomes. Caring Cross (搜索) has already advanced next-generation versions expected to enhance the potency and durability of the anti-HIV (搜索) response.
The study received funding from the California Institute for Regenerative Medicine (搜索) (CIRM) under Grant Number CLIN2-12090. The research team includes investigators from UCSF, UC Davis (搜索), and Case Western Reserve University, with manufacturing support from Vector BioMed (搜索).