CD70, a novel target of CAR T-cell therapy for gliomas

Jin, Linchun; Ge, Haitao; Long, Yu; Yang, Changlin; Chang, Ying; Mu, Lina; Sayour, Elias; Leon, Gabriel De; Wang, Qiong J.; Yang, James Chih‐Hsin; Kubilis, Paul; Bao, Hongbo; Xia, Songsong; Lu, Dunyue; Kong, Yingjun; Hu, Li; Shang, Yujiao; Jiang, Chencheng; Nie, Jing; Li, Shimin; Gu, Yue; Sun, Jing; Mitchell, Duane A.; Lin, Zhiguo; Huang, Jianping

doi:10.1093/neuonc/nox116

Cited by 151 publications

(130 citation statements)

References 36 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Cell lines engineered to produce soluble CD70 increase proliferation and IFN secretion of cocultured lymphocytes. 45 Treating in vivo murine glioma models with both a CD70 specific CAR T therapy 46 and a CD70 antibody-drug conjugate produced tumor regression. 47 However, other studies have suggested that the CD27 pathway may actually suppress T lymphocytes.…”

Section: Cd27mentioning

confidence: 99%

T lymphocyte-targeted immune checkpoint modulation in glioma

Kelly

Giles

Gilbert

2020

J Immunother Cancer

View full text Add to dashboard Cite

Immunomodulatory therapies targeting inhibitory checkpoint molecules have revolutionized the treatment of solid tumor malignancies. Concerns about whether systemic administration of an immune checkpoint inhibitor could impact primary brain tumors were answered with the observation of definitive responses in pediatric patients harboring hypermutated gliomas. Although initial clinical results in patients with glioblastoma (GBM) were disappointing, recently published results have demonstrated a potential survival benefit in patients with recurrent GBM treated with neoadjuvant programmed cell death protein 1 blockade. While these findings necessitate verification in subsequent studies, they support the possibility of achieving clinical meaningful immune responses in malignant primary brain tumors including GBM, a disease in dire need of additional therapeutic options. There are several challenges involved in treating glioma with immune checkpoint modulators including the immunosuppressive nature of GBM itself with high inhibitory checkpoint expression, the immunoselective blood brain barrier impairing the ability for peripheral lymphocytes to traffic to the tumor microenvironment and the high prevalence of corticosteroid use which suppress lymphocyte activation. However, by simultaneously targeting multiple costimulatory and inhibitory pathways, it may be possible to achieve an effective antitumoral immune response. To this end, there are now several novel agents targeting more recently uncovered “second generation” checkpoint molecules. Given the multiplicity of drugs being considered for combination regimens, an increased understanding of the mechanisms of action and resistance combined with more robust preclinical and early clinical testing will be needed to be able to adequately test these agents. This review summarizes our current understanding of T lymphocyte-modulating checkpoint molecules as it pertains to glioma with the hope for a renewed focus on the most promising therapeutic strategies.

show abstract

Section: Cd27mentioning

confidence: 99%

T lymphocyte-targeted immune checkpoint modulation in glioma

Kelly

Giles

Gilbert

2020

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…106 All of these antigens are overexpressed in glioblastoma patient specimens, and CAR-T cells targeting them reduce glioblastoma growth in mouse models. One major area of study is the identification and validation of new target antigens, including chondroitin sulphate proteoglycan 4 (CSPG4), 104 podoplanin 105 and CD70.…”

Section: Route Of Administrationmentioning

confidence: 99%

“…One major area of study is the identification and validation of new target antigens, including chondroitin sulphate proteoglycan 4 (CSPG4), 104 podoplanin 105 and CD70. 106 All of these antigens are overexpressed in glioblastoma patient specimens, and CAR-T cells targeting them reduce glioblastoma growth in mouse models. [104][105][106] Combinatorial approaches are also being explored through the development of CAR-T cells which recognise more than one target antigen.…”

Section: Route Of Administrationmentioning

confidence: 99%

“…106 All of these antigens are overexpressed in glioblastoma patient specimens, and CAR-T cells targeting them reduce glioblastoma growth in mouse models. [104][105][106] Combinatorial approaches are also being explored through the development of CAR-T cells which recognise more than one target antigen. Thus, Ahmed et al have developed tandem CAR-T cells ('TanCAR') that recognise both HER2 and IL13Ra2 via a single CAR molecule incorporating recognition domains for both antigens, as well as 'U-CAR' T cells that recognise HER2, IL-13Ra2 and EphA2 via expression of a tri-cistronic CAR transgene.…”

Section: Route Of Administrationmentioning

confidence: 99%

See 1 more Smart Citation

Clinical chimeric antigen receptor‐T cell therapy: a new and promising treatment modality for glioblastoma

2019

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR)‐T cell therapy is now approved in the United States and Europe as a standard treatment for relapsed/refractory B‐cell malignancies. It has also been approved recently by the Therapeutic Goods Administration in Australia and may soon be publicly reimbursed. This advance has accentuated scientific, clinical and commercial interest in adapting this exciting technology for the treatment of solid cancers where it is widely recognised that the challenges of overcoming a hostile tumor microenvironment are most acute. Indeed, CAR‐T cell technology may be of the greatest value for those cancers that lack pre‐existing immunity because they are immunologically ‘cold’, or have a low somatic tumor mutation load, or both. These cancers are generally not amenable to therapeutic immune checkpoint blockade, but CAR‐T cell therapy may be effective because it provides an abundant supply of autologous tumor‐specific T cells. This is achieved by using genetic engineering to re‐direct autologous T‐cell cytotoxicity towards a tumor‐associated antigen, bypassing endogenous T‐cell requirements for antigen processing, MHC‐dependent antigen presentation and co‐stimulation. One of the most challenging solid cancers is glioblastoma, which has among the least permissive immunological milieu of any cancer, and which is almost always fatal. Here, we argue that CAR‐T cell technology may counter some glioblastoma defences and provide a beachhead for furthering our eventual therapeutic aims of restoring effective antitumor immunity. Although clinical investigation of CAR‐T cell therapy for glioblastoma is at an early stage, we discuss three recently published studies, which feature significant differences in target antigen, CAR‐T cell phenotype, route of administration and tumor response. We discuss the lessons, which may be learned from these studies and which may guide further progress in the field.

show abstract

“…20,21 Additional antigens that have been proposed as GBM-associated targets for CAR T cells include EphA2, 8 chondroitin sulfate proteoglycan 4 (CSPG4), 2,11 podoplanin (PDPN), 31 the cancer stem cell antigen CD133, 35,36 and the immune-suppressive ligand CD70. 16 Clinical data are not yet available for CAR constructs targeting these antigens, though several are currently under investigation.…”

Section: Numerous Modifications and Improvements Of Existingmentioning

confidence: 99%

Chimeric antigen receptor T-cell immunotherapy for glioblastoma: practical insights for neurosurgeons

Choi¹,

Curry²,

Carter³

et al. 2018

Neurosurgical Focus

View full text Add to dashboard Cite

The prognosis for glioblastoma (GBM) remains exceedingly poor despite state-of-the-art multimodal therapy. Immunotherapy, particularly with cytotoxic T cells, represents a promising alternative. Perhaps the most prominent T-cell technology is the chimeric antigen receptor (CAR), which in 2017 received accelerated approval from the Food and Drug Administration for the treatment of hematological malignancies. Several CARs for GBM have been recently tested in clinical trials with exciting results. The authors review these clinical data and discuss areas of ongoing research.

show abstract

CD70, a novel target of CAR T-cell therapy for gliomas

Abstract: These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.

Cited by 151 publications

References 36 publications

T lymphocyte-targeted immune checkpoint modulation in glioma

T lymphocyte-targeted immune checkpoint modulation in glioma

Clinical chimeric antigen receptor‐T cell therapy: a new and promising treatment modality for glioblastoma

Chimeric antigen receptor T-cell immunotherapy for glioblastoma: practical insights for neurosurgeons

Contact Info

Product

Resources

About