Chimeric Antigen Receptors for T-Cell Malignancies

Scherer, Lauren; Brenner, Malcolm K.; Mamonkin, Maksim

doi:10.3389/fonc.2019.00126

Cited by 56 publications

(42 citation statements)

References 113 publications

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“…In addition, one more thing we want to point out based on this study, the SV 95 -specific CTLs are slightly cytotoxic to both activated HLA-A2 positive PBMCs (but not cytotoxic to normal PBMC) and hematopoietic stem cells (Figure 5C). This phenomenon has been previously reported (Leisegang et al, 2010), because the most widely expressed tumor antigen targets for malignant cells are often also expressed on non-malignant cells (Scherer et al, 2019). However, this fratricide phenomenon will not affect the space for CTLs in clinical applications but needs to be noted.…”

Section: Discussionmentioning

confidence: 70%

Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells

Chen

Jia

Zhao

et al. 2020

Front. Mol. Biosci.

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Chen et al. Novel Peptides Induce Stronger CTLs eliminated target cells (not only SV 95−1 peptide pulsed T2 cells, but also both HLA-A2 and SV positive cancer cells) when compared to those generated with natural SV 95−1 peptide and TIL2080 cells. These findings suggest that the SV 95−6 and SV 95−7 peptides are two novel HLA-A2-restricted CTL epitopes and may be useful for the immunotherapy for patients with survivin expressing cancer.

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Section: Discussionmentioning

confidence: 70%

Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells

Chen

Jia

Zhao

et al. 2020

Front. Mol. Biosci.

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“…By design, each component of the convertibleCAR system-the iNKG2D-based CAR receptor and the MicAbody (which is ADCC-deficient)-are functionally inert on their own. This has advantages during manufacturing, particularly in the context of indications such as T cell malignancies where traditional scFvbased CARs encounter expansion hurdles due to fratricide 37 . Additionally, it provides enhanced control of CAR function during treatment.…”

Section: Discussionmentioning

confidence: 99%

convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting

Landgraf¹,

Williams²,

Steiger

et al. 2020

Commun Biol

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We have developed a chimeric antigen receptor (CAR) platform that functions as a modular system to address limitations of traditional CAR therapies. An inert form of the human NKG2D extracellular domain (iNKG2D) was engineered as the ectodomain of the CAR to generate convertibleCAR TM-T cells. These cells were specifically directed to kill antigenexpressing target cells only in the presence of an activating bispecific adapter comprised of an iNKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting antibody (MicAbody TM). Efficacy against Raji tumors in NSG mice was dependent upon doses of both a rituximab-based MicAbody and convertibleCAR-T cells. We have also demonstrated that the exclusive ligand-receptor partnering enabled the targeted delivery of a mutant form of IL-2 to selectively promote the expansion of convertibleCAR-T cells in vitro and in vivo. By altering the Fv domains of the MicAbody or the payload fused to the orthogonal ligand, con-vertibleCAR-T cells can be readily targeted or regulated.

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“…By design, each component of the convertibleCAR system -the iNKG2D-based CAR receptor and the MicAbody (which is ADCC-deficient) -are functionally inert on their own. This has significant advantages during manufacturing, particularly in the context of indications such as T cell malignancies where traditional scFv-based CARs encounter expansion hurdles due to fratricide 34 . Additionally, it provides enhanced control of CAR function during treatment.…”

Section: Discussionmentioning

confidence: 99%

convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting

Landgraf

Williams

Steiger

et al. 2019

Preprint

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We have developed a chimeric antigen receptor (CAR) platform that functions as a modular system to address limitations of current CAR therapies. An inert form of the NKG2D extracellular domain (iNKG2D) was used as the ectodomain of the CAR to generate convertibleCAR™-T cells. These cells were activated only when an immunological synapse was formed with an antigenic target, mediated by a bispecific adaptor comprised of an iNKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting antibody (MicAbody TM ). Efficacy against Raji tumors in NSG mice was dependent upon doses of both a rituximabbased MicAbody and convertibleCAR-T cells. We have also demonstrated that the exclusive ligandreceptor partnering enabled the targeted delivery of a mutant form of IL-2 to exclusively promote the expansion of convertibleCAR-T cells in vitro and in vivo. By altering the Fv domains of the MicAbody or the payload fused to the orthogonal ligand, convertibleCAR-T cells can be readily targeted or regulated.

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Chimeric Antigen Receptors for T-Cell Malignancies

Cited by 56 publications

References 113 publications

Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells

Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells

convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting

convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting

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