The Retrovirus-Cell Interaction Section uses in vitro and in vivo approaches to define both the potential and the limitations of cellular immune control of AIDS virus infection.  

We focus on studies in nonhuman primate (NHP) models, using lymphocyte engineering approaches to study and optimize the ability of cellular immune responses to control AIDS virus infection. Lymphocytes are engineered for expression of SIV-specific T-cell receptors and tissue-preferential trafficking receptors. They are selected for antiviral activity to maximize the ability of the engineered cells to target and control AIDS virus infection in different experimental settings. The research holds promise for the development of bespoke immunotherapy and could illuminate the cellular immune responses, developed by vaccination or other immunotherapeutic approaches, required for effective control of AIDS virus infection. 

Optimizing cellular immunity to control AIDS viruses 

For multiple reasons, naturally occurring cellular immune responses to AIDS virus infection are suboptimal and typically fail to control the infection. We are using cellular engineering approaches in an NHP model to produce lymphocytes with antiviral activities that can specifically recognize AIDS virus-infected cells and localize to tissues where the virus replicates and persists. By infusing these engineered cells either during initial infection or at the time of discontinuation of antiretroviral drug treatment, we are evaluating the quantitative and qualitative characteristics of cellular immune responses required for effective control of AIDS virus infectionresearch with potential translational implications. 

Collaboration Opportunities

Dr. Lifson and colleagues collaborate widely with scientists within and outside the National Institutes of Health to address remaining challenges in the prevention and treatment of HIV infection and associated conditions. In addition to academic-style collaborations, external investigators can work with us through multiple established formal collaboration mechanisms, including Cooperative Research and Development Agreements (CRADA), Material Transfer Agreements (MTA), and Technical Service Agreements (TSA).

Contact Dr. Jeffrey Lifson.

Custom engineering of T lymphocytes for improved antiviral activity 

We use key advantages of well-controlled NHP models and the properties of virus-specific, receptor-engineered lymphocytes to optimize antiviral activity and define the requirements for effective viral control by cellular immunity.   

Cutting-edge technologies for optimization of anti-AIDS virus T-cell immunity 

Our work includes the optimization of intracytoplasmic signaling domains, incorporated into T-cell receptor constructs, in combinations and separately, to optimize antiviral activity. We also explore alternative cell sources for engineering beyond the most commonly employed source of peripheral blood lymphocytes. This work includes lymphocytes produced in ex vivo artificial thymic organoid cultures as the starting cell substrate to engineer for enhanced antiviral activity.   

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Directing in vivo trafficking of ex vivo engineered T cells 

Introducing tissue-preferential homing receptors into ex vivo engineered antiviral T lymphocytes helps them localize to tissues that harbor SIV in infected macaques. Specifically, the use of receptors CCR9 and CXCR5 allows cells to accumulate in the small intestine or in B-cell follicles of secondary lymphoid tissues, respectively, directing engineered cells to these sites of viral replication in primary infection and persistence in chronic infection

Our capabilities and specializations

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T-cell engineering 

We use adoptive cell therapy to understand the potential and limits of cellular immune control of AIDS virus infection. 

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  • T-cell receptor 

  • Homing receptor 

  • Viral transduction 

  • Genetic engineering 

  • Leukapheresis