568P First-in-human anti-ALPP CAR-T cell immunotherapy for ovarian and endometrial cancer

Zhu, Bao; Jia, Qingzhu; Chen, R.; Chen, G.; Zhao, L.; Palmer, N.; Xiang, Dingcheng; Chen, F.; Duan, Yaqi; Wang, H.; Shan, Jinglu; Xiong, L.; Xie, Rei; Li, G.; Yan, Liang-Jun; Li, R.; Xia, L.; Z.Su,; Alexander, P.; Li, S.

doi:10.1016/j.annonc.2022.07.696

Cited by 3 publications

(4 citation statements)

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“…[53][54][55] Alkaline phosphatase, placental type (ALPP), a cell surface protein expressed only in female reproductive tissues, has been identified as a potential target to develop a chimeric antigen receptor T cell therapy against ovarian and endometrial cancers. 56 Pre-clinical and initial clinical findings indicate that anti-ALPP chimeric antigen receptor T cell immunotherapy is potentially efficacious against female reproductive cancers expressing ALPP. 56…”

Section: Pre-clinical/phase I Study Of a Potential Target To Develop ...mentioning

confidence: 99%

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A Review of the Latest Advancements in Ovarian Cancer Care Featured at ESMO 2022

Scott¹

2023

EMJ Oncol

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Ovarian cancer is the seventh most commonly diagnosed cancer among females and the most lethal gynaecologic malignancy globally because of its vague presentation, insidious nature, recurrence, and drug resistance. There is a pressing need to improve survival and quality of life in patients with ovarian cancer in the context of rising global incidence, high risk of relapse, and poor prognosis. Presentations at the European Society for Medical Oncology (ESMO) Congress 2022 from 9th–13th September in Paris, France, showed the breadth and depth of research in ovarian cancer, including a first look at the highly anticipated data from Phase III studies on the impact on overall survival (OS) of poly(ADP-ribose) polymerase (PARP) inhibitors as first-line maintenance therapy. Clinically meaningful OS benefit was shown with olaparib at 5 years’ follow-up in PAOLA-1 and at 7 years’ follow-up in SOLO1. These positive results are a breakthrough in ovarian cancer treatment and are an important indicator that improvements in progression-free survival (PFS) may translate into OS benefits. Studies in which PARP inhibitors showed clinically meaningful efficacy, but OS data remain immature, include PRIMA, in which niraparib as a first-line maintenance therapy maintained clinically significant improvement in progression-free survival at 3.5 years’ follow-up. Research into chemotherapy resistance using a glucocorticoid receptor modulator in combination with nab-paclitaxel as part of second-line treatment showed that glucocorticoid receptor modulation can improve the efficacy of chemotherapy. Pre-clinical and early phase clinical studies are investigating a range of approaches for the treatment of ovarian cancer such as development of a chimeric antigen receptor T cell therapy, combination of a PARP inhibitor and an immune checkpoint inhibitor, and a bispecific antibody. Developments in these areas are awaited with interest. There is considerable focus on biomarkers for prognosis and progression in ovarian cancer, including research on breast related cancer antigen and homologous recombination deficiency testing, cancer antigen 125 (CA125) decline, and circulating tumour DNA (ctDNA); however, wider genetic testing, improved education of physicians on the importance of testing, and increased access to testing are recommended to optimise treatment and disease prevention. The research in ovarian cancer presented at ESMO 2022 marks important progress in this field.

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Section: Pre-clinical/phase I Study Of a Potential Target To Develop ...mentioning

confidence: 99%

“…56 Pre-clinical and initial clinical findings indicate that anti-ALPP chimeric antigen receptor T cell immunotherapy is potentially efficacious against female reproductive cancers expressing ALPP. 56…”

Section: Pre-clinical/phase I Study Of a Potential Target To Develop ...mentioning

confidence: 99%

A Review of the Latest Advancements in Ovarian Cancer Care Featured at ESMO 2022

Scott¹

2023

EMJ Oncol

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“…The First-in-Human Anti-ALPP CAR-T Cells Immunotherapy for Ovarian and Endometrial Cancer (NCT04627740) clinical trial is a single-arm, single-center, open-label study of anti-alkaline phosphatase placental (ALPP)-positive CAR-T cells [ 57 ]. The study population is patients with ALPP-positive metastatic ovarian and endometrial cancer.…”

Section: Current and Ongoing Clinical Trials For Car-t Cell Immunothe...mentioning

confidence: 99%

The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer

Choi

Kim

2023

CIMB

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Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population and patients in the metastatic setting. This discrepancy has presented an opportunity for research and development of target therapies in this population. After obtaining promising results with hematologic cancers, chimeric antigen receptor (CAR)-T cell immunotherapy is gaining acceptance as a treatment for solid neoplasms. This treatment platform allows T cells to express tumor-specific CARs on the cell surface, which are administered to the patient to treat neoplastic cells. Given that CAR-T cell therapy has shown potential and clinical benefit compared to other T cell treatment platforms, additional research is required to overcome physiological limitations such as CAR-T cell depletion, immunosuppressive tumor microenvironment, and the lack of specific target molecules. Different approaches and development are ongoing to overcome these complications. This review examines CAR-T cell therapy’s current use for endometrial carcinomas. We also discuss the significant adverse effects and limitations of this immunotherapeutic approach. Finally, we consolidate signal-seeking early-phase clinical trials and advancements that have shown promising results, leading to the approval of new immunotherapeutic agents for the disease.

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“…The study showed that 3 patients who received low-dose therapy had no cytokine release syndrome manifestations or any other CAR-T-related adverse events, suggesting a therapeutic benefit of CAR-T therapy in EC patients expressing ALPP. [51] In the absence of larger clinical studies, the application of adoptive cell immunotherapy to EC still has a long way to go.…”

Section: Namementioning

confidence: 99%

Bibliometric and visualized analysis of the top-100 highly cited articles on immunotherapy for endometrial cancer

Zheng

Wang

et al. 2023

Medicine

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Background: Immunotherapy is a promising method for the treatment of endometrial cancer (EC). We aimed to conduct a comprehensive bibliometric study of the top 100 most-cited publications on immunotherapy for EC and provide a reference for future research. Methods: Global publications on immunotherapy for EC published from 1985 to the present in the Web of Science core database were retrieved. We focused on the study of the top 100 most-cited articles by extracting information such as year, country, journal, author, institution, literature, and keywords. Microsoft Excel, VOSviewer, and R were used to perform descriptive statistics and visual analyses. Results: The top 100 most-cited articles were published between 2002 and 2022, including 70 original papers and 30 reviews. The total frequency of citations per article ranges from 15 to 287. Developed countries dominated these publications, with the United States contributing the most (50 articles). According to Bradford Law, 6 journals, including Gynecologic Oncology and the Journal of Clinical Oncology, are highly recommended. Santin A. D. from Yale University and Makker.V. from Memorial Sloan Kettering Cancer Center have made positive contributions. Among the top ten most-cited articles, 7 focused on clinical trials exploring the efficacy of immunotherapy drugs, of which 4 were lenvatinib combined with pembrolizumab for the treatment of advanced EC. The immune-microenvironment, immune antitumor mechanisms, immunomodulatory drugs, especially anti-pd-1/pd-l1 checkpoint inhibitors, and their clinical trials are the focus of current research. Conclusion: The attention of researchers from different countries to EC immunotherapy, especially immunosuppressants, has brought a breakthrough in this field. A large number of clinical trials have evaluated the efficacy and safety of immune agents, and immune combination therapy (especially targeted therapy) shows positive therapeutic promise. Immunodrug sensitivity and adverse events remain urgent issues. The key to promoting the development of EC immunotherapy is to select the best patients according to the molecular classification and immunophenotype such as tumor mutation load, MMR status, pd-l1 expression, tumor infiltrating immune cells to truly achieve accurate and personalized treatment. More new and influential EC immunotherapies, such as adoptive cell immunotherapy, still need to be explored in future clinical practice.

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568P First-in-human anti-ALPP CAR-T cell immunotherapy for ovarian and endometrial cancer

Cited by 3 publications

References 0 publications

A Review of the Latest Advancements in Ovarian Cancer Care Featured at ESMO 2022

A Review of the Latest Advancements in Ovarian Cancer Care Featured at ESMO 2022

The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer

Bibliometric and visualized analysis of the top-100 highly cited articles on immunotherapy for endometrial cancer

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