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Publications of the Week

Robust Expansion of HIV CAR T Cells following Antigen Boosting in ART-Suppressed Nonhuman Primates

By July 22, 2020No Comments

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This week we profile a recent publication in Blood from the
laboratory of Dr. Christopher William Peterson (pictured) at UW.

Can you provide a brief overview of your lab’s current research focus?

We are interested in gene and cell therapies for infectious, genetic, and malignant diseases. In particular, this publication focused on optimization of chimeric antigen receptor (CAR) T-cells for people living with HIV.

What is the significance of the findings in this publication?

Along with a number of colleagues, we were surprised to observe that virus-specific CAR T-cells were less functional in vivo, relative to CAR T-cells used for cancer. We hypothesized that the difference was due to levels of target antigen: CARs for cancer encounter very high levels of cell-associated antigen (e.g. CD19), whereas HIV-infected individuals on suppressive antiretroviral therapy (ART) have extremely low levels of antigen. To address this, we co-delivered a cell-associated antigen source, and were excited to see robust expansion of our CAR T cells and clear correlates of antiviral function.

What are the next steps for this research?

Moving forward, we’re interested in optimizing our virus-specific CAR T-cell products in many of the same ways that are being investigated in the cancer field. For example, we are following up on our findings that anti-PD1 antibodies led to transient reactivation of these cells; maintaining virus-specific immune function over a longer time frame will be important in order to protect against latently infected cells that may reactivate weeks, months, or even longer after interruption of suppressive ART. We’re also interested in further developing our antigen boosting strategy with an eye towards future clinical studies.

This work was funded by:

Our study was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (U19 HL129902), National Institute of Allergy and Infectious Diseases (UM1 AI126623, UM1 AI126617, R33 AI116184, U19 AI117945, UM1 AI126620,  and U19 AI117950), and UM1 AI126620, co-funded by NIAID, NIMH, NINDS, and NIDA.

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