Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice

Thomas, Ancy; Sumughan, Saurav; Dellacecca, Emilia R.; Shivde, Rohan; Lancki, Nicola; Mukhatayev, Zhussipbek; Vaca, Cristina C.; Han, Fei; Barse, Levi; Henning, Steven W.; Zamora-Pineda, Jesus; Akhtar, Suhail; Gupta, Nikhilesh; Zahid, Jasmine O.; Zack, Stephanie; Ramesh, Prathyaya; Jaishankar, Dinesh; Lo, Agnes S.; Moss, Joel; Picken, Maria M.; Darling, Thomas N.; Scholtens, Denise M.; Dilling, Daniel F.; Junghans, Richard P.; Poole, I. Caroline Le

doi:10.1172/jci.insight.152014

Cited by 6 publications

(2 citation statements)

References 72 publications

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“…TSC is a genetic disease that causes benign tumours to grow. The tumours mostly affect the brain, skin, kidneys, heart, and lungs 87 . To date, there is no cure for TSC, rendering anti-GD3 CAR T a valuable therapeutic option.…”

Section: Targeting Tumour-associated Carbohydrate Antigensmentioning

confidence: 99%

Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

Khilji¹,

Hoog²,

Warschkau³

et al. 2023

Theranostics

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Attached to proteins, lipids, or forming long, complex chains, glycans represent the most versatile post-translational modification in nature and surround all human cells. Unique glycan structures are monitored by the immune system and differentiate self from non-self and healthy from malignant cells. Aberrant glycosylations, termed tumour-associated carbohydrate antigens (TACAs), are a hallmark of cancer and are correlated with all aspects of cancer biology. Therefore, TACAs represent attractive targets for monoclonal antibodies for cancer diagnosis and therapy. However, due to the thick and dense glycocalyx as well as the tumour micro-environment, conventional antibodies often suffer from restricted access and limited effectiveness in vivo . To overcome this issue, many small antibody fragments have come forth, showing similar affinity with better efficiency than their full-length counterparts. Here we review small antibody fragments against specific glycans on tumour cells and highlight their advantages over conventional antibodies.

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Section: Targeting Tumour-associated Carbohydrate Antigensmentioning

confidence: 99%

Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

Khilji¹,

Hoog²,

Warschkau³

et al. 2023

Theranostics

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“…Recently developed technologies have allowed for the analyses of single-cell cytokine production in a TAA-expressing cell coculture model, leading to the assessment of CAR T cell polyfunctionality [ 52 , 53 , 54 ]. Polyfunctional CAR T cells were featured by their capability to simultaneously secrete multiple types of immune-stimulatory cytokines and cytotoxic molecules at a single-cell level [ 55 , 56 , 57 ], which can serve as a biomarker of clinical outcomes of CD19-CAR T cells [ 55 ]. A similar strategy can also be applied to measure immune-suppressive cytokines on tumor cells, supporting the investigations of adaptive resistance to immunotherapy [ 58 ].…”

Section: In Vitro Models For Car T Cell Functional Evaluationmentioning

confidence: 99%

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Xiao

Brown

et al. 2022

IJMS

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Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.

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Current state-of-the-art on ganglioside-mediated immune modulation in the tumor microenvironment

van der Haar Àvila,

Windhouwer,

van Vliet

2023

Cancer Metastasis Rev

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Gangliosides are sialylated glycolipids, mainly present at the cell surface membrane, involved in a variety of cellular signaling events. During malignant transformation, the composition of these glycosphingolipids is altered, leading to structural and functional changes, which are often negatively correlated to patient survival. Cancer cells have the ability to shed gangliosides into the tumor microenvironment, where they have a strong impact on anti-tumor immunity and promote tumor progression. Since most ganglioside species show prominent immunosuppressive activities, they might be considered checkpoint molecules released to counteract ongoing immunosurveillance. In this review, we highlight the current state-of-the-art on the ganglioside-mediated immunomodulation, specified for the different immune cells and individual gangliosides. In addition, we address the dual role that certain gangliosides play in the tumor microenvironment. Even though some ganglioside species have been more extensively studied than others, they are proven to contribute to the defense mechanisms of the tumor and should be regarded as promising therapeutic targets for inclusion in future immunotherapy regimens.

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Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice

Cited by 6 publications

References 72 publications

Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Current state-of-the-art on ganglioside-mediated immune modulation in the tumor microenvironment

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