Phase I experience with first in class TnMUC1 targeted chimeric antigen receptor T-cells in patients with advanced TnMUC1 positive solid tumors.

Gutierrez, Rodolfo; Shah, Payal D.; Hamid, Omid; Garfall, Alfred L.; Posey, Avery D.; Bishop, Michael; Blumenschein, George R.; Johnson, Melissa L.; Lee, Sylvia; Luke, Jason J.; Morgensztern, Daniel; Fountaine, Thomas J.; Dryer-Minnerly, Rebecca; Najmi, Saltanat; Hufner, Pam; Chagin, Karen

doi:10.1200/jco.2021.39.15_suppl.e14513

Cited by 23 publications

(13 citation statements)

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“…In addition, a multi-center first-in-human phase I clinical trial investigated the safety and efficacy of TnMUC1-CAR T-cells with CD2 costimulatory domain in the treatment of 6 patients with TnMUC positive solid tumors including metastatic treatment-resistant ovarian cancer, pancreatic adenocarcinoma, TNBC, or NSCLC. They found that CAR T-cells were expanded in all patients, particularly those who had undergone lymphodepleting chemotherapy with fludarabine and cyclophosphamide, and that the intervention was safe, with no on-target/off-tumor toxicity (NCT04025216) ( 78 ). The efficacy of the treatment is scheduled to be evaluated in a second expansion phase that encompasses 72 more patients.…”

Section: Target Antigens For Car T-cell Therapy Of Solid Tumors In Cl...mentioning

confidence: 99%

The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies

et al. 2023

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The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.

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Section: Target Antigens For Car T-cell Therapy Of Solid Tumors In Cl...mentioning

confidence: 99%

The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies

et al. 2023

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“…95 Similarly, stable disease (achieved in 3 of 6 treated subjects) was the best response achieved using CAR T-cells specific for the Tn glycoform of MUC1. 105…”

Section: Clinical Experience Of Car T-cell Immunotherapy Of Lung Cancermentioning

confidence: 99%

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Patients with Lung Cancer: Current Perspectives

Maher¹

2023

OTT

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Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved unprecedented efficacy in selected hematological cancers. However, solid tumors such as lung cancer impose several additional challenges to the attainment of clinical success using this emerging therapeutic modality. Lung cancer is the biggest cause of cancer-related mortality worldwide, accounting for approximately 1.8 million deaths worldwide each year. Obstacles to the development of CAR T-cell immunotherapy for lung cancer include the selection of safe tumor-selective targets, accounting for the large number of candidates that have been evaluated thus far. Tumor heterogeneity is also a key hurdle, meaning that single target-based approaches are susceptible to therapeutic failure through the emergence of antigen null cancers. There is also a need to enable CAR T-cells to traffic efficiently to sites of disease, to infiltrate tumor deposits and to operate within the hostile tumor microenvironment formed by solid tumors, resisting the onset of exhaustion. Multiple immune, metabolic, physical and chemical barriers operate at the core of malignant lesions, with potential for further heterogeneity and evolution in the face of selective therapeutic pressures. Although the extraordinarily adaptable nature of lung cancers has recently been unmasked, immunotherapy using immune checkpoint blockade can achieve long-term disease control in a small number of patients, establishing clinical proof of concept that immunotherapies can control advanced lung carcinomas. This review summarizes pre-clinical CAR T-cell research that is specifically focused on lung cancer in addition to published and ongoing clinical trial activity. A number of advanced engineering strategies are also described which are designed to bridge the gap to the attainment of meaningful efficacy using genetically engineered T-cells.

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“…The investigators propose to evaluate safety and preliminary antitumor activity in patients with metastatic MUC1*-positive breast cancer [322]. Moreover, a multicentric clinical trial is evaluating a CART-TnMUC1 immunotherapy in solid tumors (triple-negative breast cancer, epithelial ovarian cancer, pancreatic cancer, and non-small cell lung cancer) and TnMUC1 positive multiple myeloma, designed to identify the dose and regimen at which CART-TnMUC1 cells can be safely administered intravenously following lymphodepletion (NCT04025216) [330]. In a second expansion phase enrolling 72 more patients, efficacy is due to be assessed.…”

Section: Car-t Cells Targeting Gd2mentioning

confidence: 99%

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives

Berois

Pittini

Osinaga

2022

Cancers

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Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis antigens, and polysialic acid. In this review, we analyze strategies for cancer immunotherapy targeting TACAs, including different antibody developments, the production of vaccines, and the generation of CAR-T cells. Some approaches have been approved for clinical use, such as anti-GD2 antibodies. Moreover, in terms of the antitumor mechanisms against different TACAs, we show results of selected clinical trials, considering the horizons that have opened up as a result of recent developments in technologies used for cancer control.

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Phase I experience with first in class TnMUC1 targeted chimeric antigen receptor T-cells in patients with advanced TnMUC1 positive solid tumors.

Cited by 23 publications

References 0 publications

The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies

The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Patients with Lung Cancer: Current Perspectives

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives

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