Health
CAR-NKT cell therapy shows promising results against neuroblastoma in phase 1 clinical trial
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HOUSTON – (May 15, 2023) – Researchers at Baylor College of Medicine/Texas Children’s Cancer Center and collaborating institutions report interim results from a first-in-human phase 1 clinical trial evaluating the safety, antitumor activity and immunological characteristics of a genetically engineered natural killer T (NKT) cell immunotherapy for neuroblastoma, a childhood tumor that most commonly arises in the adrenal gland. The study published in Nature Medicine shows the treatment was well tolerated, and researchers observed early evidence of strong antitumor activity.
NKT cells were modified to express a GD2-specific chimeric antigen receptor (GD2 CAR), which enables the immune cells to target a molecule found on the surface of neuroblastoma cells, and interleukin-15 (IL-15), a natural protein that supports NKT cell survival. In a previous Nature Medicine publication, the authors reported interim results from the first three children enrolled on this trial.
In the new article, investigators describe the results obtained in 12 patients with stage 4 relapsed neuroblastoma that was resistant to other therapies. They found that the therapy was safe for all 12 patients on four dose levels; there were no reported no dose-limiting toxicities. Three patients showed an objective response to treatment, including one complete response and two partial responses. Two other patients also showed evidence of antitumor activity such as clearance of bone marrow involvement or reduction of metastatic tumor burden not reaching partial response criteria.
“We are encouraged by the evidence of antitumor activity that has been observed in several patients, particularly since this trial is still in the dose escalation phase,” said Dr. Andras Heczey, co-corresponding author and associate professor of pediatrics – hematology and oncology at Baylor. He also is a member of the Center for Advanced Innate Cell Therapy at Texas Children’s Cancer Center, the Center for Cell and Gene Therapy at Baylor and Texas Children’s and the Dan L Duncan Comprehensive Cancer Center at Baylor.
Previous studies from the team have shown that NKT cells can localize to tumor sites in pre-clinical models. This trial has validated those observations in humans. Additionally, researchers found a correlation between higher antitumor activity and in vivo proliferation of infused CAR-NKT cells.
“We cannot always predict the extent of NKT cell expansion in vivo after infusion,” said Dr. Leonid Metelitsa, co-corresponding author and professor of pediatrics – hematology and oncology at Baylor. “In this study, we found the CD62L biomarker expressed on the infused NKT cells, which we identified in our preclinical work, is predictive of both higher NKT cell in vivo expansion and antitumor activity in patients.” Metelitsa is also director of the Center for Advanced Innate Cell Therapy at Texas Children’s Cancer Center and a member of the Center for Cell and Gene Therapy at Baylor and Texas Children’s and the Dan L Duncan Comprehensive Cancer Center at Baylor.
Another important finding revealed a regulatory gene in NKT cells that may impact the efficacy of treatment. Leveraging the multiomic platform of key collaborator Immunai, Inc., Baylor researchers found that upregulation of the BTG anti-proliferation factor 1 (BTG1) gene in infused CAR NKT cells is indicative of cell exhaustion and restricts CAR NKT cell functional activity. Conversely, engineered reduction of BTG1 expression in CAR NKT cells enhanced their therapeutic activity against neuroblastoma in a mouse model.
“This study provides promising initial evidence of antitumor activity of GD2 CAR NKT cells against neuroblastoma. This inspires hope that novel immunotherapeutic strategies, such as the one studied in this trial, will ultimately improve the outcomes for children with neuroblastoma,” Metelitsa said.
Based on the safety profile and promising evidence of antitumor activity, this trial has been expanded to include two higher dose levels for the GD2 CAR NKT cells. Following completions of these additional cohorts, a phase 2 trial to assess the antitumor activity of this novel immunotherapeutic is planned.
Other contributors to this work include Xin Xu, Amy N. Courtney, Gengwen Tian, Gabriel A. Barragan, Linjie Guo, Claudia Martinez Amador, Nisha Ghatwai, Purva Rathi, Michael S. Wood, Yanchuan Li, Chunchao Zhang, Thorsten Demberg, Erica J. Di Pierro, Andrew C. Sher, Huimin Zhang, Birju Mehta, Sachin G. Thakkar, Bambi Grilley, Tao Wang, Brian D. Weiss, Antonino Montalbano, Meena Subramaniam, Chenling Xu, Chirag Sachar, Daniel K. Wells and Gianpietro Dotti. The authors are affiliated with the following institutions: Baylor College of Medicine, Texas Children’s Hospital, Cincinnati Children’s Hospital, Immunai, Inc., and University of North Carolina at Chapel Hill.
This work was supported by Alex’s Lemonade Stand Foundation for Childhood Cancer, St. Baldrick’s Foundation, the American Cancer Society and Athenex, Inc. For a full list of author affiliations and funding for this work, refer to the publication.
# # #
Journal
Nature Medicine
Article Title
Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results
Article Publication Date
15-May-2023
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
Health
CFIA continues surveillance for HPAI in cattle, while sticking with original name for disease – RealAgriculture
The Canada Food Inspection Agency will continue to refer to highly pathogenic avian influenza in cattle as HPAI in cattle, and not refer to it as bovine influenza A virus (BIAV), as suggested by the American Association of Bovine Practitioners earlier this month.
Dr. Martin Appelt, senior director for the Canadian Food Inspection Agency, in the interview below, says at this time Canada will stick with “HPAI in cattle” when referencing the disease that’s been confirmed in dairy cattle in multiple states in the U.S.
The CFIA’s naming policy is consistent with the agency’s U.S. counterparts’, as the U.S. Animal and Plant Health Inspection Service has also said it will continue referring to it as HPAI or H5N1.
Appelt explains how the CFIA is learning from the U.S. experience to-date, and how it is working with veterinarians across Canada to stay vigilant for signs of the disease in dairy and beef cattle.
As of April 19, there has not been a confirmed case of HPAI in cattle in Canada. Appelt says it’s too soon to say if an eventual positive case will significantly restrict animal movement, as is the case with positive poultry cases.
This is a major concern for the cattle industry, as beef cattle especially move north and south across the U.S. border by the thousands. Appelt says that CFIA will address an infection in each species differently in conjunction with how the disease is spread and the threat to neighbouring farms or livestock.
Currently, provincial dairy organizations have advised producers to postpone any non-essential tours of dairy barns, as a precaution, in addition to other biosecurity measures to reduce the risk of cattle contracting HPAI.
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Health
Toronto reports 2 more measles cases. Use our tool to check the spread in Canada – Toronto Star
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Canada has seen a concerning rise in measles cases in the first months of 2024.
By the third week of March, the country had already recorded more than three times the number of cases as all of last year. Canada had just 12 cases of measles in 2023, up from three in 2022.
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Cancer Awareness Month
Posted on: Apr 18, 2024
April is Cancer Awareness Month
As we recognize Cancer Awareness Month, we stand together to raise awareness, support those affected, advocate for prevention, early detection, and continued research towards a cure. Cancer is the leading cause of death for Métis women and the second leading cause of death for Métis men. The Otipemisiwak Métis Government of the Métis Nation Within Alberta is working hard to ensure that available supports for Métis Citizens battling cancer are culturally appropriate, comprehensive, and accessible by Métis Albertans at all stages of their cancer journey.
Receiving a cancer diagnosis, whether for yourself or a loved one, can feel overwhelming, leaving you unsure of where to turn for support. In June, our government will be launching the Cancer Supports and Navigation Program which will further support Métis Albertans and their families experiencing cancer by connecting them to OMG-specific cancer resources, external resources, and providing navigation support through the health care system. This program will also include Métis-specific peer support groups for those affected by cancer.
With funding from the Canadian Partnership Against Cancer (CPAC) we have also developed the Métis Cancer Care Course to ensure that Métis Albertans have access to culturally safe and appropriate cancer services. This course is available to cancer care professionals across the country and provides an overview of who Métis people are, our culture, our approaches to health and wellbeing, our experiences with cancer care, and our cancer journey.
Together, we can make a difference in the fight against cancer and ensure equitable access to culturally safe and appropriate care for all Métis Albertans. Please click on the links below to learn more about the supports available for Métis Albertans, including our Compassionate Care: Cancer Transportation program.
I wish you all good health and happiness!
Bobbi Paul-Alook
Secretary of Health & Seniors
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