T-Bodies as Antiviral Agents

Bitton, Natacha; Debré, Patrice; Eshhar, Zelig; Gorochov, Guy

doi:10.1007/978-3-662-05783-4_14

Cited by 4 publications

(2 citation statements)

References 207 publications

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“…Here, we show that cytotoxicity of NK‐92 cells against lymphoblastic target cells, including cell lines, ALL‐LTCs and primary ALL cells is effectively restored after their transfection with a CAR against CD19. This approach was originally developed to bypass MHC‐restriction in genetically modified T cells, and has been investigated in this setting for a number of surface antigens expressed on cancer cells or viruses . Several phase I studies with CD19‐CAR modified T cells have shown complete and partial remissions .…”

Section: Discussionmentioning

confidence: 99%

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

Romański

Uherek

Bug

et al. 2016

J Cellular Molecular Medi

198

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Many B‐cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK‐92 cells, a continuously growing NK cell line, showing that anti‐CD19‐CAR (αCD19‐CAR) engineered NK‐92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK‐92 cells. The ‘first generation’ CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3ζ chain and a Myc‐tag and cloned into a retrovirus backbone. No difference in cytotoxic activity of NK‐92 and transduced αCD19‐CAR NK‐92 cells towards CD19 negative targets was found. However, αCD19‐CAR NK‐92 cells specifically and efficiently lysed CD19 expressing B‐precursor leukaemia cell lines as well as lymphoblasts from leukaemia patients. Since NK‐92 cells can be easily expanded to clinical grade numbers under current Good Manufactoring Practice (cGMP) conditions and its safety has been documented in several phase I clinical studies, treatment with CAR modified NK‐92 should be considered a treatment option for patients with lymphoid malignancies.

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Section: Discussionmentioning

confidence: 99%

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

Romański

Uherek

Bug

et al. 2016

J Cellular Molecular Medi

198

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“…From the earliest days (Bitton et al, 2001) until the present (Kuhlmann et al, 2018;Wagner, 2018;Kim et al, 2019;Liu et al, 2019;Mylvaganam et al, 2019), CD4 has been a favored component for the targeting domain of anti-HIV CARs, because it recognizes an essential conserved feature of gp120 that presumably must be retained for viral persistence and pathogenicity. Our group has reported improved bispecific designs of CD4-based CARs containing a second moiety that targets a distinct conserved determinant on gp120 (Liu et al, 2015;Ghanem et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

A Trispecific Anti-HIV Chimeric Antigen Receptor Containing the CCR5 N-Terminal Region

Hajduczki

Danielson

Elias

et al. 2020

Front. Cell. Infect. Microbiol.

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Anti-HIV chimeric antigen receptors (CARs) promote direct killing of infected cells, thus offering a therapeutic approach aimed at durable suppression of infection emerging from viral reservoirs. CD4-based CARs represent a favored option, since they target the essential conserved primary receptor binding site on the HIV envelope glycoprotein (Env). We have previously shown that adding a second Env-binding moiety, such as the carbohydrate recognition domain of human mannose-binding lectin (MBL) that recognizes the highly conserved oligomannose patch on gp120, increases CAR potency in an in vitro HIV suppression assay; moreover it reduces the undesired capacity for the CD4 of the CAR molecule to act as an entry receptor, thereby rendering CAR-expressing CD8 + T cells susceptible to infection. Here, we further improve the bispecific CD4-MBL CAR by adding a third targeting moiety against a distinct conserved Env determinant, i.e. a polypeptide sequence derived from the N-terminus of the HIV coreceptor CCR5. The trispecific CD4-MBL-R5Nt CAR displays enhanced in vitro anti-HIV potency compared to the CD4-MBL CAR, as well as undetectable HIV entry receptor activity. The high anti-HIV potency of the CD4-MBL-R5Nt CAR, coupled with its all-human composition and absence of immunogenic variable regions associated with antibody-based CARs, offer promise for the trispecific construct in therapeutic approaches seeking durable drug-free HIV remission.

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Quarter Century of Anti-HIV CAR T Cells

Wagner

2018

Curr HIV/AIDS Rep

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Research on anti-HIV chimeric antigen receptor T cells has been going on for at least the last 25 years. First- and second-generation anti-HIV chimeric antigen receptors have been developed. First-generation anti-HIV chimeric antigen receptors were studied in clinical trials more than 15 years ago, but did not have meaningful clinical efficacy. There are some reasons to be optimistic about second-generation anti-HIV chimeric antigen receptor T cells, but they have not yet been tested in vivo.

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T-Bodies as Antiviral Agents

Cited by 4 publications

References 207 publications

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

A Trispecific Anti-HIV Chimeric Antigen Receptor Containing the CCR5 N-Terminal Region

Quarter Century of Anti-HIV CAR T Cells

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