Tag Archives: lung cancer

Dogs inhale new immunotherapy to fight lung cancer

Posted on June 12, 2022 | Leave a comment

A protein that the body naturally produces could become an important new immunotherapy drug in the cache of cancer-fighting tools available to oncologists. UC Davis cancer researchers for both companion dogs and humans joined scientists from other institutions to study a new approach that triggers the body’s defense mechanisms, its T-cells and natural killer (NK) cells, to respond and destroy cancer.

Oncologist Robert Canter said an inhaled immunotherapy for dogs with cancer shows promise for human cancer patients.

Surgical oncologist Robert J. Canter with UC Davis Comprehensive Cancer Center and canine oncologist Robert B. Rebhun with the UC Davis School of Veterinary Medicine are corresponding authors for a study just published in the Journal for ImmunoTherapy of Cancer.

In the first-of-its-kind Phase 1 clinical trial, 21 pet dogs of various breeds that had metastatic lung disease resulting from osteosarcoma or melanoma were treated with protein interleukin-15 (IL-15). Although previously recognized for immunotherapy properties, IL-15 has undergone few human clinical trials because of toxicity risks associated with concentrated doses.

“No one previously had administered IL-15 as an inhaled treatment in dogs to deliver it directly to the site of the cancer. We came up with that idea as a means of reducing exposure to the rest of the body, in order to improve the benefit-risk ratio, to improve the immune stimulating effects, and to reduce toxicity,” Canter explained. “In this study, we used interleukin-15 to reinvigorate the immune system to make it recognize the cancer cells that had evaded the immune system and eliminate them.”

The research shows that amplified concentrations of IL-15 can stimulate immune system defenses against some types of cancers in dogs. IL-15 is one of several types of cytokines—substances that have signaling and regulating functions in immune system activity.

“As part of our comparative oncology research, we are strong advocates of clinical trials in companion dogs, especially for immunotherapy, as a way to speed bench-to-bedside translation,” said Canter, who is chief of the UC Davis Division of Surgical Oncology and co-director of the comparative oncology training program at UC Davis. “The cancers that afflict dogs, including sarcomas, brain tumors, lymphoma and melanoma, are incredibly similar to cancers that humans develop.”

UC Davis received a $2 million National Cancer Institute grant to fund the comparative oncology training program to support the next generation of oncology researchers collaborating on curing cancer in both humans and dogs. For instance, osteosarcoma and melanoma that develop elsewhere in the body commonly spread to the lung, in dogs as well as humans.

Methodology

In the study, conducted between October 2018 and December 2020, the dogs inhaled a mist containing IL-15 twice daily. Doses were increased over time, to help determine not only effectiveness, but also tolerable levels and the ceilings above which toxicity would result. Dogs exhibited significant responses within 14 days after they began inhaling the IL-15 mist.

Tumors shrank dramatically in two dogs in the study, including one that went into complete remission for more than a year. Cancer that had been growing rapidly in five other dogs stabilized for several months. “Our overall response rate, the clinical benefit rate, was close to 40%,” Canter said.

For that and other reasons, additional studies are needed, noted Rebhun, a professor in the UC Davis School of Veterinary Medicine’s Department of Surgical and Radiological Sciences.

“The inhaled IL-15 responses that we’ve seen in dogs are better than prior human studies, but clinical benefit is seen in less than half of the dogs. Using IL-15 in people has led to potentially favorable immune responses but has not yielded good tumor responses. This indicates that combining IL-15 with other immunotherapies may result in additive or synergistic responses,” said Rebhun, who holds the Maxine Adler Endowed Chair in Oncology and is the associate director of the cancer program in the Center for Companion Animal Health.

Key findings

In his view, the study yielded two significant findings: the therapy was well tolerated, and even a short two-week course of inhaled IL-15 could lead to sustained suppression of advanced and diffuse metastatic cancer. Both he and Canter noted that in eventual clinical application, IL-15 likely would be used not as a standalone therapy, but as a reinforcement in combination with other treatments.

“All of the canine patients in this study had advanced metastatic cancer, and the majority already had received prior chemotherapy, radiation therapy and, in some cases, immunotherapy. Studies are ongoing now to see whether we can predict which patients might respond to this therapy based on properties of the tumor or the patient’s immune status,” Rebhun said.

“This may help us identify patients that might respond to this therapy, as well as help us understand how to potentially combine other immunotherapies to improve response rates. We are grateful to the extremely dedicated clients who sought any and all possible care for their pets, elected to enroll them in this study, and even delivered the inhaled IL-15 to their dogs at home—in hopes that it could benefit their dog, other dogs, or possibly even people with advanced metastatic cancer,” Rebhun said.

Other authors of the study included UC Davis researchers Daniel York, Sylvia M. Cruz and Sean J. Judge, along with Colorado State University scientists Rachel V. Brady and Jenna H. Burton, and Louisiana State University researcher Sita S. Withers.

As part of the grant for the study, the National Institutes of Health supplied the recombinant IL-15, which it expressed from source materials. The study was supported in part by National Institutes of Health and the National Cancer Institute.

Source: UC Davis

Dogs with lung cancer may get gene-directed treatment with the same drug used to combat a type of human breast cancer

Posted on August 27, 2019 | Leave a comment

Despite those velvet paintings of poker-playing dogs smoking pipes, cigars and cigarettes, our canine friends really don’t use tobacco. But like many humans who have never smoked, dogs still get lung cancer. photo-for-her2-study

And, like many women who develop a particular type of breast cancer, the same gene — HER2 — also appears to be the cause of lung cancer in many dogs, according to a promising new study of pet dogs led by the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope, and The Ohio State University.

Published in the journal Clinical Cancer Research, this study could have significant implications for people who have never smoked.

TGen and Ohio State found that neratinib — a drug that has successfully been used to battle human breast cancer — might also work for many of the nearly 40,000 dogs in the U.S. that annually develop the most common type of canine lung cancer, known as canine pulmonary adenocarcinoma, or CPAC.

Neratinib inhibits a mutant cancer-causing form of the gene HER2, which is common to both CPAC and HER2-positive human breast cancer patients.

“With colleagues at Ohio State, we found a novel HER2 mutation in nearly half of dogs with CPAC. We now have a candidate therapeutic opportunity for a large proportion of dogs with lung cancer,” said Dr. Will Hendricks, an Assistant Professor in TGen’s Integrated Cancer Genomics Division, Director of Institutional Research Initiatives, and the study’s senior author.

Based on the results from this study, a clinical trial using neratinib is planned for dogs with naturally occurring lung cancer that have the HER2 mutation.

“This is the first precision medicine clinical trial for dogs with lung cancer. That is, the selection of cancer therapy for a particular patient is based on the genomic profile of the patient’s tumor and matched with agents that are known to specially target the identified mutation,” said Dr. Wendy Lorch, an Associate Professor in the Department of Veterinary Clinical Sciences at The Ohio State University College of Veterinary Medicine, who also will run the study’s clinical trial.

“Our team at The Ohio State University has worked for years to find treatments for canine lung cancer. This breakthrough shows the value of these studies for dogs, as well as humans with lung cancer who never smoked,” said Dr. Lorch, who also is the study’s lead author.

CPAC is an aggressive disease that clinically resembles human lung cancer among never-smokers. There is no standard-of-care treatment for CPAC and — prior to the work performed by the TGen-Ohio State team — little was known of the disease’s genetic underpinnings.

“These results are the first example of our efforts to adapt genomics tools from the human world, such as gene sequencing and liquid biopsies, to generate novel insights in canine cancers, with mutual benefit for both,” said Dr. Muhammed Murtaza, Assistant Professor and Co-Director of TGen’s Center for Noninvasive Diagnostics, and one of the study’s contributing authors.

While the sequencing of hundreds of thousands of human cancer genomes has driven the transformational development of precise targeted cancer treatments for humans over the past decade, relatively few canine cancer genomes have undergone similar profiling. The canine cancer genomic discovery and drug development efforts of the TGen-Ohio State team are pieces of a larger puzzle that could similarly transform veterinary oncology, while creating bridges between canine and human cancer drug development.

“This study is groundbreaking because it not only identified a recurring mutation in a canine cancer that had never been found before, but it actually led directly to a clinical trial,” said Dr. Jeff Trent, TGen President and Research Director, and one of the study’s contributing authors. “This clinical translation from dog to human and back is the holy grail of comparative cancer research.”

Lung cancer is the leading cause of cancer death in the U.S., annually taking the lives of more than 154,000 Americans.

“This study is really exciting to us because, not only have we found a recurrent hot-spot mutation in a canine cancer that had never been found before, but it actually has direct clinical translational relevance. For humans, we already have drugs that can inhibit many dysregulated proteins. We hope to show that we can provide the same benefit for dogs with canine cancers,” Dr. Hendricks added.

No dogs were harmed in this study. Only pet dogs with naturally occurring cancer were examined.

This study — Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma — lays the foundation for potential rapid translational development. Follow-up clinical and genomic studies have been funded in part by a $300,000 grant investment from the Petco Foundation made possible through their 10-year Pet Cancer Campaign in partnership with Blue Buffalo. Susanne Kogut, President of The Petco Foundation, said her organization’s investment in the next phase of TGen-Ohio State studies is part of a larger effort to improve the health and welfare of pets everywhere.

“We are so excited to be a part of this study of canine lung cancer, which we hope will rapidly benefit our pet, and pet-parent, communities worldwide,” said Kogut, who in 2016 was named one of 25 “women of influence” by Pet Age magazine.

Source: TGen meda release

Clinical trials to help beat cancer

Posted on June 28, 2016 | 2 comments

Raelene Wouda’s passion for improving cancer treatment starts with our four-legged friends.

Dog cancer photo
Wouda, Kansas State University assistant professor of clinical sciences, is conducting clinical trials to treat cancers in dogs, cats and other companion animals.

When pet owners bring their dogs, cats, horses and other animals to the College of Veterinary Medicine’s Veterinary Health Center for treatment, Wouda and the Oncology Service can offer groundbreaking new treatments often at a lower cost to pet owners.

Wouda also is able to study important topics, such as improved diagnostic testing, monitoring approaches and innovative treatment options, including anti-cancer vaccines, t-cell transfer, combination chemotherapy and nanoparticle drug formulations. She has recently published her research in Veterinary Comparative Oncology and the Journal of the American Veterinary Medical Association.

“Although surgery, radiation therapy, chemotherapy and, more recently, immunotherapy have improved patient outcomes, many cancers still do not have a long-term cure,” said Wouda, a clinical veterinary oncologist. “These clinical trials are a crucial step.”

But Wouda’s research benefits humans, too. Many cancers in animals — especially dogs — are similar to those in humans, which means that the diagnosis, monitoring, treatment and response to treatment are also similar.

“Any research that we do in our patients has the potential to provide important information for how the disease can be better diagnosed, monitored and treated in human patients,” Wouda said. “That’s what I would like to do with our research. I would like to continue to improve outcomes for our veterinary patients and, by extension, help human cancer patients.”

Companion animals offer several research advantages. Wouda’s clinical trial program focuses primarily on dogs because of the similarities between their cancers and human cancers, such as osteosarcoma, melanoma, lung cancer and urogenital cancers. Osteosarcoma, for example, is both clinically and genetically almost identical in dogs and human pediatric patients.

Dogs also live with us and are exposed to the same environmental factors. Additionally, because dogs age faster than humans — one dog year is equivalent to seven human years — their diseases progress faster, which is a practical advantage for rapidly evaluating a new treatment’s efficacy and clinical benefit, Wouda said.

“We get clinical answers more quickly in dogs,” Wouda said. “The benefit of a particular therapy becomes evident in dogs more rapidly compared to people, and because of this we can preserve research and development finances, but more importantly, we save valuable time and resources.”

Animal clinical trials are structured similarly to human clinical trials and are tightly regulated and overseen. Wouda works with Mary Lynn Higginbotham, associate professor of clinical sciences, their graduate students and oncology technicians as well as the Veterinary Health Center’s referring veterinarians to conduct these clinical trials. They also collaborate with human medical researchers to discuss how the research can best be applied in the field of human oncology.

“For many pet owners, cancer is a terminal diagnosis for their beloved family member,” Wouda said. “These studies provide owners an opportunity to trial a cutting-edge therapy for their pets at a reasonable price. Moreover, owners participating in these clinical trials take comfort and are pleased to know that they are helping to achieve better treatments and outcomes for pets that may be diagnosed with cancer in the future.”

Source: Kansas State University

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Posted in Dogs, research

Tagged cancer, Kansas State University, lung cancer, melanoma, oncology, osteosarcoma, Raelene Wouda