Last update 19 Sep 2024

Endodermal Sinus Tumor

Last update 19 Sep 2024

Basic Info

Synonyms

ENDODERMAL SINUS TUMOR, Embryonal carcinoma, infantile, Embryonal carcinoma, infantile type

+ [44]

Introduction

An unusual and aggressive tumor of germ-cell origin that reproduces the extraembryonic structures of the early embryo. It is the most common malignant germ cell tumor found in children. It is characterized by a labyrinthine glandular pattern of flat epithelial cells and rounded papillary processes with a central capillary (Schiller-Duval body). The tumor is rarely bilateral. Before the use of combination chemotherapy, the tumor was almost invariably fatal. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1189)

Clinical Trials associated with Endodermal Sinus Tumor

NCT06198296 / Not yet recruitingPhase 1IIT

Immunotherapy For Adults With GPC3-Positive Solid Tumors Using Interleukin-15 And -21 Armored Glypican-3-Specific Chimeric Antigen Receptor Expressing Autologous T Cells

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells.
Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise but have not been strong enough to cure most patients.
In order to get them to kill cancers more effectively, in the laboratory, the study team inserted a new gene called a chimeric antigen receptor (CAR) into T cells that makes them recognize cancer cells and kill them. When inserted, this new CAR T cell can specifically recognize a protein found on solid tumors, called glypican-3 (GPC3). To make this GPC3-CAR more effective, the study team also added two genes called IL15 and IL21 that help CAR T cells grow better and stay in the blood longer so that they may kill tumors better. When the study team did this in the laboratory, they found that this mixture of GPC3-CAR,IL15 and IL21 killed tumor cells better when compared with CAR T cells that did not have IL15 plus IL21 in the laboratory. This study will use those cells, which are called 21.15.GPC3-CAR T cells, to treat patients with solid tumors that have GPC3 on their surface.
The study team also wanted to make sure that they could stop the 21.15.GPC3-CAR T cells from growing in the blood should there be any bad side effects. In order to do so, they inserted a gene called iCasp9 into the FAST-CAR T cells. This allows us the elimination of 21.15.GPC3-CAR T cells in the blood when the gene comes into contact with a medication called AP1903. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. This drug will only be used to kill the T cells if necessary due to side effects .
The study team has treated patients with T cells that include GPC3. Patients have also been treated with IL-21 and with IL-15. Patients have not been treated with a combination of T cells that contain GPC3, IL-21 and IL-15. To summarize, this study will test the effect of 21.15.GPC3-CAR T cells in patients with solid tumors that express GPC3 on their surface.
The 21.15.GPC3-CAR T cells are an investigational product not yet approved by the Food and Drug Administration.

Start Date01 Jan 2026

Sponsor / Collaborator

Baylor College of Medicine

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NCT04715191 / Not yet recruitingPhase 1IIT

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T Cells as an Immunotherapy for Children With Solid Tumors (CARE)

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called CARE T cells, a new experimental treatment.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.
Investigators have found from previous research that they can put a new gene (a tiny part of what makes-up DNA and carries a person's traits) into T cells that will make them recognize cancer cells and kill them. In the lab, investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GPC3. The antibody GPC3 recognizes a protein found solid tumors including pediatric liver cancers. This CAR is called GPC3-CAR. To make this CAR more effective, investigators also added two genes that includes IL15 and IL21, which are protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 plus IL21 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15 plus IL21 .This study will test T cells that investigators made (called genetic engineering) with GPC3-CAR and the IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors.
T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigators will insert the iCasp9 and IL15 plus IL21 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects.
This study will test T cells genetically engineered with a GPC3-CAR and IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors.
The CARE T cells are an investigational product not approved by the Food and Drug Administration.
The purpose of this study is to find the biggest dose of CARE T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the CARE T cells will help people with GPC3-positive solid tumors.

Start Date03 Jul 2024

Sponsor / Collaborator

Baylor College of Medicine

[+1]

NCT06427941 / Not yet recruitingPhase 1

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Selected Advanced or Metastatic Solid Tumors

This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of the BGB-B2033 in participants with advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors, non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC). The study will also identify the recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab for subsequent proof-of-concept studies. BGB-B2033 will be administered by intravenous infusion. The Phase 1 study will be conducted in 2 parts: Part A (Monotherapy Dose Escalation and Safety Expansion) and Part B (Combination Dose Escalation and Safety Expansion).

Start Date23 May 2024

Sponsor / Collaborator

BeiGene Ltd.

100 Clinical Results associated with Endodermal Sinus Tumor

100 Translational Medicine associated with Endodermal Sinus Tumor

0 Patents (Medical) associated with Endodermal Sinus Tumor

2,724

Literatures (Medical) associated with Endodermal Sinus Tumor

20 Feb 2024·International journal of surgical pathology

Retroperitoneal Sarcomatoid Yolk Sac Tumor in a Chemotherapy-Naive Patient With Testicular Postpubertal Type Teratoma: A Rare Case Report With Emphasis on Molecular Features.

Article

Author: Bo Zhang ; Payal Kapur ; Prasad R Koduru ; Liwei Jia

Sarcomatoid yolk sac tumor is a very rare histologic type of testicular germ cell tumor and is mainly reported in testicular germ cell tumor patients who receive chemotherapy. Herein, we report an extremely rare concurrent retroperitoneal sarcomatoid yolk sac tumor in a man with a testicular postpuberal teratoma before he received chemotherapy. A 37-year-old man initially presented with a persistent abdominal pain. Subsequent imaging studies revealed a 9.6-cm retroperitoneal mass, and 2 testicular masses (3.1 cm and 0.9 cm in greatest dimension, respectively). His serum tumor markers were within normal ranges. His radical orchiectomy demonstrated a postpubertal type teratoma with an adjacent scarring nodule. Later, his retroperitoneal tumor showed spindle tumor cells embedded in predominantly myxoid and focally fibrous stroma with diffuse and strong immunoreactivity for keratin AE1/AE3, SALL4 and glypican 3. No tumor necrosis or brisk mitotic figures were observed. A diagnosis of sarcomatoid yolk sac tumor was rendered. Fluorescence in situ hybridization analysis of his retroperitoneal sarcomatoid yolk sac tumor revealed polysomy 12 and MYC amplification, whereas no evidence of isochromosome 12p [i(12p)], and DNA sequencing showed 6 mutations per megabase (muts/Mb), and the somatic alterations included ARAF amplification and ATR I774Yfs*5. Considering its rarity, sarcomatoid yolk sac tumor may pose diagnostic challenges. Therefore, relevant clinicoradiologic information and ancillary work up, including immunohistochemistry and molecular studies, may be helpful for the accurate classification. Our tumor further raises awareness of this rare event, expands the spectrum of its clinical presentation, and explores the molecular features.

12 Feb 2024·BMC urology

46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report.

Article

Author: Changrong Wang ; Jiangli Du ; Xueping Xiang ; Yuyong Wang ; Jingjing Xiang ; Qiaoping Xu

BACKGROUND:

Extragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis.

CASE PRESENTATION:

A 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels.

DISCUSSION:

A case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

11 Feb 2024·European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

Review

Author: Anas Dabsha ; Ismail A M H Elkharbotly ; Mohammad Yaghmour ; Amr Badr ; Fady Badie ; Sherif Khairallah ; Yomna M Esmail ; Mohamed Hossny ; Amr Rizk ; Amr El-Demiry ; Galal Ghaly ; Shaikha Al-Thani ; Michelle Demetres ; Abdelrahman Mohamed ; Jonathan Villena-Vargas ; Mona Kamal ; Mohamed Rahouma

BACKGROUND:

Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST.

METHODS:

Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586).

RESULTS:

Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS.

CONCLUSION:

Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

News (Medical) associated with Endodermal Sinus Tumor

13 Jan 2021

·www.biospace.com

Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid Tumors

CAMBRIDGE, Mass., Jan. 13, 2021 (GLOBE NEWSWIRE) -- Cytovia Therapeutics an emerging biopharmaceutical company focusing on Natural Killer cells in cancer, announced today that it has signed a licensing agreement with the National Cancer Institute (NCI), part of the National Institutes of Health, to apply its gene-edited iPSC-derived NK cell technology to develop GPC3 CAR NK cell therapeutics. Dr Mitchell Ho, PhD, Director of the Antibody Engineering Program and Deputy Chief of the Laboratory of Molecular Biology at the NCI Center for Cancer Research has developed novel antibodies and chimeric antigen receptors (CAR) binding to glypican-3 (GPC3) on liver cancer cells. Dr. Ho has published data on the humanized GPC3 antibody in scientific reports (nature research) in 2016 as well as on the GPC3 CAR in Gastroenterology in 2020. GPC3 is an oncofetal antigen involved in Wnt-dependent cell proliferation. It is highly expressed in Hepatocellular Carcinoma tumor cells as well as multiple other solid tumors, including ovarian cancer and lung cancer, but not expressed in adult normal tissues. Cytovia has also signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute. Under the CRADA, Cytovia will collaborate with Dr. Ho’s laboratory to develop and evaluate gene-edited iPSC-derived GPC3 CAR NK cells. Cytovia expects to initial new drug application (IND) for its GPC3 CAR NK cells in the first half of 2022. Dr. Daniel Teper, Chairman and CEO of Cytovia Therapeutics commented: “GPC3 is an exciting new validated target for Hepatocellular Carcinoma, an area of major unmet medical need, as well as other solid tumors. We look forward to collaborating with Dr. Ho, a pioneer in GPC3 research, to develop a novel gene-edited, iPSC-derived GPC3 CAR NK that will advance toward a cure for liver cancer.” Dr. Ho added: “Natural Killer cells play a major role in the immuno-surveillance of liver cancer. GPC3 is expressed in more than 70% of Hepatocellular Carcinoma cells but not on healthy cells. We look forward to investigating whether GPC3 CAR-NK therapy could provide a new safe and effective off-the-shelf option for patients with liver cancer.” ABOUT GENE-EDITED, IPSC-DERIVED NK CELLS Chimeric Antigen Receptors (CAR) are fusion proteins that combine an extracellular antigen recognition domain with an intracellular co-stimulatory signaling domain. Natural Killer (NK) cells are modified genetically to allow insertion of a CAR. CAR-NK cell therapy has demonstrated initial clinical relevance without the limitations of CAR-T, such as Cytokine Release Syndrome, neurotoxicity or Graft vs Host Disease (GVHD). In addition, CAR-NKs are naturally allogeneic, available off-the-shelf and may be able to be administered on an outpatient basis. Recent innovative developments with the induced pluripotent stem cell (iPSC)-derived CAR-NKs, an innovative technology, allow large quantities of homogeneous genetically modified CAR NK cells to be produced from a gene-edited iPSC master cell bank, and thus hold promise to expand access to cell therapy for many patients. ABOUT HCC Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of death worldwide, with 800,000 new cases diagnosed globally every year. The incidence in Asia is amongst the highest in the world (75%) with 400,000 in China alone. In the US, it is estimated to reach upwards of 30,000 by the end of 2020 and continues to be on the rise. Despite advances in immunotherapy, with current treatment options including multi-kinase inhibitors (TKI) and checkpoint inhibitors, life expectancy for patients diagnosed with HCC remains very low. The disease is often diagnosed at an advanced stage, with a median survival of approximately 6 to 20 months following diagnosis, and a 5-year survival rate below 10% in the US. Fortunately, new options including cell therapy and bispecific antibodies offer promise towards a cure for liver cancer. ABOUT GPC3 Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan expressed in the liver and the kidney of fetuses but is hardly expressed in adults, except in the placenta. However, it is highly expressed in HCC, ovarian clear cell carcinoma, squamous cell carcinoma of the lung, melanoma, hepatoblastoma, nephroblastoma (Wilms tumor), yolk sac tumor, and some pediatric cancers. GPC3 promotes Wnt-dependent cell proliferation and has been strongly suggested that it is related to the malignant transformation. Therefore, GPC3 is a promising target for cancer immunotherapy and can serve as a biomarker for predicting tumor recurrence and treatment efficacy. About Cytovia Therapeutics Cytovia Therapeutics Inc is an emerging biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem, INSERM, and CytoImmune Therapeutics. Learn more at and follow Cytovia Therapeutics on Social Media (Facebook, LinkedIn, Twitter, and Youtube). Contact for investor enquiries: Anna Baran-Djokovic Vice President, Investor Relations Anna@cytoviatx.com 1 (646) 355 1787

CollaborateSmall molecular drugAntibodyCell TherapyImmunotherapy

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