NK cells with bispecific antibody show activity against lymphoma cells
Preclinical study supports clinical trial of cord blood-derived natural killer cells with Affimed's AFM13 as novel cellular therapy
2021-05-13
(Press-News.org) HOUSTON - Cytokine-activated natural killer (NK) cells derived from donated umbilical cord blood, combined with an investigational bispecific antibody targeting CD16a and CD30 known as AFM13, displayed potent anti-tumor activity against CD30+ lymphoma cells, according to a new preclinical study from researchers at The University of Texas MD Anderson Cancer Center.
The findings were published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. These results led to the launch of a Phase I clinical trial to evaluate the combination of cord blood-derived NK cells (cbNK cells) with AFM13 as an experimental cell-based immunotherapy in patients with CD30+ lymphoma.
"Developing novel NK cell therapies has been a priority for my team at MD Anderson to address unmet needs for the treatment of both hematologic cancers and solid tumors," said senior author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy. "This preclinical work provided proof of principle for NK cells precomplexed with AFM13, suggesting that they can effectively eliminate lymphoma cells expressing CD30 and warrant further clinical testing."
Natural killer cells are part of the innate immune system and work naturally to eliminate cancer cells in the body. However, they have limited persistence on their own, and tumors can develop mechanisms to evade NK cells, Rezvani explained. Therefore, her research team has worked to develop approaches to enhance the anti-tumor efficacy of NK cells.
Affimed's AFM13 is a proprietary bispecific antibody designed to bind to CD16a on NK cells and CD30 on lymphoma cells. Initial studies on NK cells isolated from the blood of patients with Hodgkin lymphoma found that AFM13 formed a stable complex with NK cells and could induce NK cell-mediated killing of CD30+ cells. However, the activity of these cells was modest, leading the researchers to evaluate alternative NK cell sources.
Further experiments suggested that cbNK cells, isolated from umbilical cord blood donations made to the MD Anderson Cord Blood Bank, displayed consistent and improved activity against lymphoma with AFM13 relative to other NK cell sources. The researchers were able to further stimulate the anti-tumor immune activity of cbNK cells by pre-activation with a combination of the cytokines IL-12/15/18.
In animal models, pre-activated and expanded cbNK cells complexed with AFM13 resulted in improved tumor control and survival relative to controls, with minimal side effects observed.
"These findings suggest that, in animal models, ex vivo pre-activated and expanded cord blood-derived NK cells complexed with AFM13 were able to safely eliminate CD30+ lymphoma cells," Rezvani said. "We look forward to learning if this investigational therapy may provide benefits to patients with advanced lymphoma in the ongoing clinical trial."
INFORMATION:
Interim results on three patients from the Phase I clinical trial were presented by Rezvani at the virtual American Association for Cancer Research (AACR) 2021 Annual Meeting. The trial is ongoing.
This research was supported in part by the National Institute of Health (NIH) (1 R01 CA211044-01, 5 P01CA148600-03, P50CA100632-16, CA016672, K12CA167540 and R01CA205239), the National Cancer Institute (NCI) (P30CA091842), the NIH/NCI SPORE in Leukemia (P50CA171963) and Affimed. A full list of collaborating authors and their disclosures can be found here.
MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan.
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
2021-05-13
WASHINGTON -- In a new study, researchers have shown that 3D printing can be used to make highly precise and complex miniature lenses with sizes of just a few microns. The microlenses can be used to correct color distortion during imaging, enabling small and lightweight cameras that can be designed for a variety of applications.
"The ability to 3D print complex micro-optics means that they can be fabricated directly onto many different surfaces such as the CCD or CMOS chips used in digital cameras," said Michael Schmid, a member of the research team from University of Stuttgart in Germany. "The micro-optics can ...
2021-05-13
CORVALLIS, Ore. - Free from human disturbance for a century, an inland island in Central America has nevertheless lost more than 25% of its native bird species since its creation as part of the Panama Canal's construction, and scientists say the losses continue.
The Barro Colorado Island extirpations show how forest fragmentation can reduce biodiversity when patches of remnant habitat lack connectivity, according to a study by researchers at Oregon State University.
Even when large remnants of forest are protected, some species still fail to survive because of subtle ...
2021-05-13
DALLAS - May 12, 2021 - Scientists with UT Southwestern's Peter O'Donnell Jr. Brain Institute have identified the molecular mechanism that can cause weight gain for those using a common antipsychotic medication. The findings, published in the Journal of Experimental Medicine, suggest new ways to counteract the weight gain, including a drug recently approved to treat genetic obesity, according to the study, which involved collaborations with scientists at UT Dallas and the Korea Advanced Institute of Science and Technology.
"If this effect can be shown in clinical trials, it could give us a way to effectively treat ...
2021-05-13
Astronomers commonly refer to massive stars as the chemical factories of the Universe. They generally end their lives in spectacular supernovae, events that forge many of the elements on the periodic table. How elemental nuclei mix within these enormous stars has a major impact on our understanding of their evolution prior to their explosion. It also represents the largest uncertainty for scientists studying their structure and evolution.
A team of astronomers led by May Gade Pedersen, a postdoctoral scholar at UC Santa Barbara's Kavli Institute for Theoretical Physics, have now measured the internal mixing within an ensemble of these stars using observations ...
2021-05-13
Leesburg, VA, May 13, 2021--According to an open-access Editor's Choice article in ARRS' American Journal of Roentgenology (AJR), CT features may help identify which patients with stage IA non-small cell lung cancer are optimal candidates for sublobar resection, rather than more extensive surgery.
This retrospective study included 904 patients (453 men, 451 women; mean age, 62 years) who underwent lobectomy (n=574) or sublobar resection (n=330) for stage IA non-small cell lung cancer. Two thoracic radiologists independently evaluated findings on preoperative chest CT, later resolving any discrepancies. Recurrences were identified via medical record review.
"In patients with stage IA non-small cell lung cancer, pathologic ...
2021-05-13
Boston - Pregnant women with symptomatic COVID-19 have a higher risk of intensive care unit admissions, mechanical ventilation and death compared to non-pregnant reproductive age women. Increases in preterm birth and still birth have also been observed in pregnancies complicated by the viral infection. The Centers for Disease Control and Prevention (CDC) recommended that people who are pregnant may choose to be vaccinated at their own discretion with their healthcare provider. However, pregnant and lactating women were not included in Phase 3 vaccine efficacy trials; thus, data on vaccine safety and immunogenicity in this population is limited.
In a new study from Beth Israel Deaconess Medical Center (BIDMC), ...
2021-05-13
Despite having been driven nearly to extinction, the California condor has a high degree of genetic diversity that bodes well for its long-term survival, according to a new analysis by University of California researchers.
Nearly 40 years ago, the state's wild condor population was down to a perilous 22. That led to inbreeding that could have jeopardized the population's health and narrowed the bird's genetic diversity, which can reduce its ability to adapt to changing environmental conditions.
In comparing the complete genomes of two California condors with those of an Andean condor and a turkey vulture, UC San Francisco and UC Berkeley scientists did find genetic evidence of inbreeding over the past few centuries, but, overall, a ...
2021-05-13
TORONTO, ON - A team of evolutionary biologists from the University of Toronto has shown that Anolis lizards, or anoles, are able to breathe underwater with the aid of a bubble clinging to their snouts.
Anoles are a diverse group of lizards found throughout the tropical Americas. Some anoles are stream specialists, and these semi-aquatic species frequently dive underwater to avoid predators, where they can remain submerged for as long as 18 minutes.
"We found that semi-aquatic anoles exhale air into a bubble that clings to their skin," says Chris Boccia, a recent Master of Science graduate from the Faculty of Arts & Science's Department of Ecology ...
2021-05-13
Traffic noise leads to inaccuracies and delays in the development of song learning in young birds. They also suffer from a suppressed immune system, which is an indicator of chronic stress. A new study by researchers of the Max Planck Institute for Ornithology and colleagues shows that young zebra finches, just like children, are particularly vulnerable to the effects of noise because of its potential to interfere with learning at a critical developmental stage.
Traffic noise is a pervasive pollutant that adversely affects the health and well-being ...
2021-05-13
New Orleans, LA - Research conducted by an international team of scientists discovered a mechanism that leads to Herceptin resistance, representing a significant clinical obstacle to successfully treating HER2-positive breast cancer. They also identified a new approach to potentially overcome it. The work is published online in Nature Communications, available here.
"This work attempts to understand why some HER2-positive breast cancer patients do not benefit from treatment with Herceptin, which is a generally effective HER2-targeted therapy," explains Bolin Liu, MD, Professor of Genetics at LSU Health New Orleans' School of Medicine and Stanley S. Scott Cancer Center.
The researchers found increased signaling by IGF2/IRS1 (genes involved in ...
LAST 30 PRESS RELEASES:
[Press-News.org] NK cells with bispecific antibody show activity against lymphoma cells
Preclinical study supports clinical trial of cord blood-derived natural killer cells with Affimed's AFM13 as novel cellular therapy
