CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression

Fousek, Kristen; Watanabe, Junji; Joseph, Sujith; George, Ann; An, Xingyue; Byrd, Tiara; Morris, Jessica S.; Luong, Annie; Martínez-Paniagua, Melisa; Sanber, Khaled; Navai, Shoba A.; Gad, Ahmed Z.; Salsman, Vita S.; Mathew, Pretty; Kim, Hye Na; Wagner, Dimitrios L.; Brunetti, Lorenzo; Jang, Albert; Baker, Matthew L.; Varadarajan, Navin; Hegde, Meenakshi; Kim, Yong-Mi; Heisterkamp, Nora; Abdel‐Azim, Hisham; Ahmed, Nabil

doi:10.1038/s41375-020-0792-2

Cited by 117 publications

(81 citation statements)

References 55 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After promising in vitro studies which showed success in targeting CD19− escape B-ALL cells, in vivo mouse models were used to investigate the efficacy of CD19/20/22 CAR T cell therapy on targeting CD19+ and CD19− escape malignancies. Treatments of CD19/20/22 CAR T cells showed significant anti-tumour response in both mouse models with CD19+ B-ALL as well as the CD19− escape B-ALL which CD19 CAR T cells was ineffective at treating alone [24]. This method presents an exciting branch of CAR T cell therapy for haematological B cell malignancies which do not express CD19.…”

Section: Limitations Of Car T Cell Therapy For Haematological Cancersmentioning

confidence: 94%

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Alard

Butnariu

Grillo

et al. 2020

Cancers

View full text Add to dashboard Cite

Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient’s own immune system to selectively kill cancer cells. The immune system is the body’s main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recognise tumour neoantigens, inactivating immune checkpoints, oncolytic viruses and dendritic cell (DC) vaccines, which have all shown clinical benefit in certain cancers. However, treatment efficacy remains poor due to drug-induced adverse events and immunosuppressive tendencies of the tumour microenvironment. Recent preclinical studies have unveiled novel therapies such as anti-cathepsin antibodies, galectin-1 blockade and anti-OX40 agonistic antibodies, which may be utilised as adjuvant therapies to modulate the tumour microenvironment and permit more ferocious anti-tumour immune response.

show abstract

Section: Limitations Of Car T Cell Therapy For Haematological Cancersmentioning

confidence: 94%

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Alard

Butnariu

Grillo

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…There are two patterns of trivalent CAR T-cells: TriCAR expressing CD19 CAR, CD20 CAR, and CD22 CAR on a single T-cell and side CAR expressing CD20/CD19 TanCAR combined with CD19 CAR ( 31 ). Fousek et al ( 172 ) constructed CD19/CD20/CD22 TriCAR T-cells that manifested strong killing activity on both ALL cells and CD19-negative relapsed cells in vitro and in murine models, while CD19 CAR T-cells were ineffective.…”

Section: Clinical Strategiesmentioning

confidence: 99%

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Huang

Xiao

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

show abstract

“…Indeed, one 8-year old patient received sequential treatments of anti-CD19 CAR, followed by anti-CD22 CAR resulting in partial response, subsequently followed by anti-CD20 CAR which cleared the cancer to complete remission [ 34 ]. Rather than giving each of these treatments sequentially, a recent CAR construct was designed to transduce donor T-cells with CD19, CD20 and CD22 targeting CARs in the same cell [ 35 ], thus cells that lose expression of one of the lineage markers would still be cleared by the adoptively transferred CARs.…”

Section: Loss Of Car Antigenmentioning

confidence: 99%

T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road

Crowther

Svane

Met

2020

Cells

View full text Add to dashboard Cite

T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the “off-the-shelf” capabilities of these genetic engineering methods.

show abstract

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression

Cited by 117 publications

References 55 publications

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road

Contact Info

Product

Resources

About