At Rezvani Lab in MD Anderson Cancer Center, scientists train immune cells to fight cancer. Photo via Getty Images

Unique cell therapy developed in Houston doses inaugural patient

cancer-fighting innovation

Replay, a genome-writing company headquartered in San Diego, has announced that its first patient has been dosed with an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma.

What does that have to do with Houston? Last year, Replay incorporated a first-in-class engineered TCR-NK cell therapy product company, Syena, using technology developed by Dr. Katy Rezvani at The University of Texas MD Anderson Cancer Center.

Rezvani, a professor of stem cell transplantation and cellular therapy, is the force behind MD Anderson’s Rezvani Lab, a group of 55 people, all focused on harnessing natural killer cells to combat cancer.

“Everybody thinks that the immune system is fighting viruses and infections, but I feel our immune system is capable of recognizing and killing abnormal cells or cells that are becoming cancerous and they're very powerful. This whole field of immunotherapy really refers to the power of the immune system,” Rezvani tells InnovationMap.

Dr. Katy Rezvani is a professor of stem cell transplantation and cellular therapy and the force behind MD Anderson’s Rezvani Lab, which is focused on harnessing natural killer cells to combat cancer. Photo via mdanderson.org

At Rezvani Lab, scientists train immune cells to fight cancer. While cancer drugs like chemotherapy are still the norm, immunotherapy has gained ground, led by Houston research, including the work of Nobel laureate Jim Allison. The harnessed cells are taught to attack cancerous cells, while ignoring healthy ones, says Rezvani. “We’re turning them into heat-seeking missiles,” she explains.

However, there must be a beacon to signal to those “missiles” that there is something to attack. Much of the field has used chimeric antigen receptors (CARs) to achieve that. But they have limitations.

“CARs can only recognize beacons that sit on the surface of the tumor cells,” Rezvani says. “So basically, it's like the tumor cell has to have a hat on it.”

She says that this usually means that the targets that send off a signal are relatively limited, mostly blood cancers. Using T cell receptors (TCRs) may be able to open up the field to look beyond the “hat.” In other words, TCRs can peer inside cells and see what differentiates a tumor cell from healthy cells. With Replay, Rezvani Lab has developed a first-in-class and first-in-human approach of engineering natural killer cells to express the TCR.

There are six different FDA-approved products that use CAR-T cells, but Rezvani says that her TCR-NK-based technology, though still in its early phases, shows great promise.

“We could use it to target many different types of antigens, many different types of cancers, especially solid tumors," she explains. "These cell therapies have a lot of potential — we call them living drugs… It's not like chemotherapy where you have to keep giving different multiple cycles, these cells are very long lived.”

Rezvani, who started her career in London, says that Houston has been instrumental in the success of her lab.

“There are so many opportunities because we have access to some of the most brilliant minds in research,” Rezvani says. “We have some of the best clinicians in the world. We have patients who come to us who are willing to participate in our clinical trials — really put their trust in us — and are committed and want to participate in these clinical studies.”

The role of funding also plays a part. As Rezvani admitted, bringing a new technology to the market is expensive. The philanthropists who help support trials can’t be forgotten among Houston’s finest.

Whether or not Syena produces the first TCR-NK product on the market, Rezvani is enthusiastic and hopeful for the future of her patients.

“The field of immunotherapy is really expanding, the field of cell therapies is expanding, and there is so much promise,” she says. “The promise of AI, big data, all the engineering tools that we have available, the promise of CRISPR — all of that is going to bring what we've learned from biology, from basic science, together to help us make the cell therapies that are going to be safe and and also very effective for our patients.”

A Houston health care company received the green light from the FDA to advance a treatment that's targeting a deadly cancer. Photo via Getty Images

Houston immunotherapy company achieves FDA designation for cancer-fighting vaccine

got the green light

The FDA has granted a Houston-based company a Fast Track designation.

Diakonos Oncology Corp. is a clinical-stage immuno-oncology company that has developed a unique dendritic cell vaccine, DOC1021. The vaccine targets glioblastoma multiforme (GBM), the most common and most lethal malignant brain tumor in adults. The aggressive tumors come with a life expectancy of about 15 months following diagnosis. About 7 percent of those diagnosed survive five years, while the 10-year outlook only sees a one-percent survival rate.

“The FDA’s decision acknowledges the potential of this new treatment approach for a very challenging disease,” Diakonos CEO Mike Wicks says in a press release. “Our protocol represents a first for cancer immunotherapy and could be viable for many types of cancers beyond GBM.”

FDA Fast Track designations are intended to expedite the haste with which drugs with early clinical promise are reviewed, likely taking them to market faster.

DOC1021 uses the body’s natural anti-viral immune response to fight GBM. The vaccine mimics viral infection with the patient’s cancer markers. Essentially, DOC1021 uses the body’s own natural ability to detect and eliminate infected cells.

The technology uses dendritic cells, white blood cells that are able to perceive threats, to its advantage. The unique cancer markers are loaded both internally and externally into the immune cells, just as they would simultaneously occur in a viral infection. The individualized treatment is administered through three precise injections that target deep cervical lymph node chains. By dosing this way, the immune responses are directed straight to the central nervous system.

The results have spoken for themselves: All of the patients who have tried the treatment have exceeded survival expectations. And just as importantly, DOC1021 appears to be extremely safe. No serious adverse effects have been reported.

“Because Phase I clinical trials are generally not statistically powered to demonstrate efficacy, detection of a statistically significant efficacy signal is very promising,” says William Decker, associate professor of immunology at Baylor College of Medicine and inventor of the DOC1021 technology.

The Phase 1 open-label trial of DOC1021 (NCT04552886) is currently taking place at both the University of Texas Health Science Center in Houston and at the MD Anderson Cancer Center at Cooper University Health Care in Camden, NJ. The trial is expected to complete this year.

7 Hills Pharma, an innovative immunotherapy company, was awarded a $13.5 million grant from the Cancer Prevention and Research Institute of Texas. Photo via Getty Images

Houston immunotherapy company to use $13.5M grant to further develop cancer treatments

future of pharma

Between Bangalore and Chennai in the Indian state of Andhra Pradesh, you’ll find the town of Tirupati. It’s home to seven peaks that host a Hindu temple complex devoted to a form of Vishnu, Venkateshvara. It is also the region from which Upendra Marathi originally hails. It’s where his father, and many other family members, attended medical school.

“My father’s first job was to take care of the pilgrims,” recalls Marathi.

It's only natural that his groundbreaking Houston company would be named 7 Hills Pharma.

“That sort of selflessness and giving back, I wanted to embody it in the name of the company,” Marathi says.

Now, 7 Hills Pharma is announcing that last month, it was awarded a $13.5 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT). That’s on top of more than $13 million in NIH grants, making the company the second largest recipient of SBIR/STTR grants in Texas.

Launched in 2016, 7 Hills Pharma is working to develop drugs that can overcome the all-too-common problem of immunotherapy resistance. Thanks to the Nobel Prize-winning work of Jim Allison in the realm of immuno-oncology, the field was “very hot” at the time, says Marathi, particularly in Houston.

So what has 7 Hills developed? Oral small molecules that activate integrins — the receptors that allow cells to bind to one another — allowing for the cell-to-cell interactions that create a successful immune response to immune checkpoint inhibitors such as Yervoy. In other words, they have created capsules that increase the effectiveness of drugs that allow the body’s own immune response to fight cancers.

But that’s not all. Tests have shown that the same discovery, called alintegimod, can also augment the effectiveness of vaccines. The pill, which co-founder and co-inventor Peter Vanderslice calls “a beautiful way to amplify the vaccines,” can potentially be applied to anything from influenza to coronavirus.

Their greatest challenge, says Vanderslice, is the very fact that the technology is so novel.

“Most large pharmas are very risk averse,” he explains. “They only want to do ‘me-too’ kinds of drugs.”

7 Hills Pharma is the third company Marathi, both a PhD and an MBA, has helped to found based on technology he co-invented. Vanderslice is director of the molecular cardiology research laboratories at The Texas Heart Institute.

“It’s very much a homegrown company,” Marathi says.

And a small one, at least for now. Working out of JLabs@TMC, the full-time team is currently just Marathi and Siddhartha De, the senior director of development. Marathi convinced De to transplant himself and his family from India for the purpose of assisting 7 Hills with preparing its drugs for clinical readiness.

The CPRIT funds will allow 7 Hills Pharma to hire several long-time team members full-time and with benefits.

“The bringing of talent and bringing of technology to TMC and what was born at Texas Heart Institute is rather remarkable,” says Rob Bent, the company’s director of operations.

The next step for 7 Hills Pharma is a Phase Ib/IIa clinical trial in patients with treatment-resistant solid tumors. And the team just finalized the deck that will help raise another $10 million to $250 million in the company’s series A. And hopefully sooner rather than later, a new set of medical pilgrims will be thanking 7 Hill Pharma for its care.

A UH professor is fighting cancer with a newly created virus that targets the bad cells and leaves the good ones alone. Photo via Getty Images

University of Houston researchers snag $1.8M to develop cancer-fighting virus

immunotherapy innovation

Viruses attack human cells, and that's usually a bad thing — some Houston researchers have received fresh funding to develop and use the evil powers of viruses for good.

The developing cancer treatment is called oncolytic virotherapy and has risen in popularity among immunotherapy research. The viruses can kill cancer cells while being ineffective to surrounding cells and tissue. Basically, the virus targets the bad guys by "activating an antitumor immune response made of immune cells such as natural killer (NK) cells," according to a news release from the University of Houston.

However exciting this rising OV treatment seems, the early stage development is far from perfect. Shaun Zhang, director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston, is hoping his work will help improve OV treatment and make it more effective.

“We have developed a novel strategy that not only can prevent NK cells from clearing the administered oncolytic virus, but also goes one step further by guiding them to attack tumor cells. We took an entirely different approach to create this oncolytic virotherapy by deleting a region of the gene which has been shown to activate the signaling pathway that enables the virus to replicate in normal cells,” Zhang says in the release.

Zhang, who is also a M.D. Anderson professor in the Department of Biology & Biochemistry, has received a $1.8 million grant from the National Institutes of Health to continue his work.

Zhang and his team are specifically creating a new OV — called FusOn-H2 and based on the Herpes simplex 2 virus.

“Our recent studies showed that arming FusOn-H2 with a chimeric NK engager (C-NK-E) that can engage the infiltrated natural killer cells with tumor cells could significantly enhance the effectiveness of this virotherapy,” he says. “Most importantly, we observed that tumor destruction by the joint effect of the direct oncolysis and the engaged NK cells led to a measurable elicitation of neoantigen-specific antitumor immunity.”

Shaun Zhang is the director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston and M.D. Anderson professor in the Department of Biology & Biochemistry. Image via UH.edu

Houston's Nobel Prize winner, Jim Allison, is the star of Breakthrough, which premieres on Independent Lens at 9 pm Monday, April 27, on PBS, PBS.org, and the PBS Video App. Photo via SXSW.com

Documentary featuring Houston Nobel Prize winner to air on PBS

to-watch list

Not all heroes wear capes. In fact, our current coronavirus heroes are donning face masks as they save lives. One local health care hero has a different disease as his enemy, and you'll soon be able to stream his story.

Dr. James "Jim" Allison won the 2018 Nobel Prize in Physiology or Medicine for his work in battling cancer by treating the immune system — rather than the tumor. Allison, who is the chair of Immunology and executive director of the Immunotherapy Platform at MD Anderson Cancer Center, has quietly and often, singularly, waged war with cancer utilizing this unique approach.

The soft-spoken trailblazer is the subject of an award-winning documentary, Jim Allison: Breakthrough, which will air on PBS and its streaming channels on Monday, April 27 at 9 pm (check local listings for channel information). Lauded as "the most cheering film of the year" by the Washington Post, the film follows Allison's personal journey to defeat cancer, inspired and driven by the disease killed his mother.

Breakthrough is narrated by Woody Harrelson and features music by Willie Nelson, adding a distinct hint of Texana. (The film was a star at 2019's South by Southwest film festival.) The documentary charts Alice, Texas native as he enrolls at the University of Texas, Austin and ultimately, cultivates an interest in T cells and the immune system — and begins to frequent Austin's legendary music scene. Fascinated by the immune system's power to protect the body from disease, Allison's research soon focuses on how it can be used to treat cancer.

Viewers will find Allison charming, humble, and entertaining: the venerable doctor is also an accomplished blues harmonica player. Director Bill Haney weaves Allison's personal story with the medical case of Sharon Belvin, a patient diagnosed with melanoma in 2004 who soon enrolled in Allison's clinical trials. Belvin has since been entirely cancer-free, according to press materials.

"We are facing a global health challenge that knows no boundaries or race or religion, and we are all relying on gifted and passionate scientists and healthcare workers to contain and ultimately beat this thing," said Haney, in a statement. "Jim Allison and the unrelenting scientists like him are my heroes – and I'll bet they become yours!"

Jim Allison: Breakthrough premieres on Independent Lens at 9 pm Monday, April 27, on PBS, PBS.org, and the PBS Video App.

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This article originally ran on CultureMap.

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Houston researchers develop breakthrough device that could bypass spinal injuries

breakthrough research

Scientists at Houston Methodist have announced a significant leap forward for spinal cord injury recovery.

The researchers have developed a device that essentially bypasses spinal injuries, allowing signals from previously “lost” functions to reach the brain, a new study published in Nature Communications shows.

“Most current technologies try to improve whatever function remains after a spinal cord injury,” Dr. Damiano Barone, assistant professor of neurosurgery in the Department of Neurosurgery at Houston Methodist and co-lead on the study, said in a news release. “Our goal is different. Rather than fixing the injury itself, we want to bypass it completely and create an alternative route for signals to travel.”

The study involved a single ultrathin circumferential electrode array made to conform around the spinal cord without penetrating neural tissue, which was implanted into rodent and pig models with spinal injuries. The electrode array was able to interpret motor, sensory and autonomic signals around the injury. Think of it as a set of detours that restore road access to isolated towns after a disaster destroys the highway instead of just rebuilding the highway.

Over the course of three days, the arrays detected signals of intended movement from low-frequency spinal oscillations with more than 94 percent accuracy. This worked across species and was replicated in feasibility studies on human cadavers.

This research could serve as a new foundation for neuroprosthetic implants that could restore connectivity to the 2.5 million people worldwide suffering from spinal injuries that result in loss of ability. Future development could result in everything from restored organ function to mobility, according to Houston Methodist.

George Malliaras, the Prince Professor of Technology in the Department of Engineering at the University of Cambridge, who co-led the study, sees it as a fundamental restructuring of the science of spinal trauma.

“This could represent a paradigm change in how we think about spinal cord injuries,” Malliaras said. “Instead of starting from the idea that what is lost is gone forever, this approach asks whether we can restore function by carrying the signal around the injury.”

Further work involving laboratory models will need to be completed before launching human trials.

Grants from the National Institutes of Health, Houston Methodist Katz Investigator Award, Helaers Research Award and the Engineering and Physical Sciences Research Council helped support the study. Other collaborators on the study include Salim Hadwe, Ruben Serrano, George Psaltakis, Margaux Forner, Chaeyeon Lee, Sydney Swedick, Moleca Ghnnam, Tawfique Hasan and Alejandro Carnicer-Lombarte from the University of Cambridge; and Anton Banta and Xueer Zhang from Houston Methodist.

Abbott assembles expert team to help lure U.S. Space Academy to Texas

space race

State Rep. Greg Bonnen of Friendswood has been tapped to lead a new team that will promote Texas as the future home of the U.S. Space Academy.

Bonnen, a neurosurgeon, chairs Houston Physicians’ Hospital and the powerful Texas House Appropriations Committee. His House district is close to NASA’s Johnson Space Center.

Gov. Greg Abbott appointed the seven-member team. Last month, President Trump signed an executive order establishing the Presidential Commission on the U.S. Space Academy. Commission members, who held their first meeting this month, will recommend a permanent location for the academy.

Texas officials are pushing a site near Johnson Space Center to host the academy. Alabama, Colorado and Florida are among Texas’ competitors.

In a joint statement, U.S. Sen. Ted Cruz and U.S. Rep. Brian Babin, both of Texas, issued a statement backing the state’s bid for the academy. Cruz lives in Houston. Babbin lives in Woodville, about 55 miles south of Beaumont.

“America’s space program is built across the country, but Texas is where the pieces come together,” the lawmakers said. “We are ready to lead the next generation of space pioneers and look forward to showing why Texas is the right home for the U.S. Space Academy.”

The academy’s curriculum will include technical education, leadership development and public service components. Graduates will be set up for careers in the U.S. military, civil service, and aerospace sectors.

The Abbott-appointed team will work with the Texas Space Commission to prepare the state’s proposal for the academy.

In addition to Bonnen, team members with ties to Houston include:

  • Robert Ambrose, who grew up in Houston. He worked at Johnson Space Center before becoming associate director of the Texas A&M Space Institute.
  • Former NASA astronaut Nancy Curry-Gregg, director of the Texas A&M Space Institute. She earned a doctoral degree from the University of Houston and previously worked at Johnson Space Center.
  • Former NASA astronaut Jack Fischer, senior vice president of Houston-based Intuitive Machines. The company builds spacecraft, delivers payloads to the moon and launches satellites.

“Texas is the home of America’s human spaceflight program,” Abbott said in a release. “No state can match what Texas brings to this mission.”

“NASA’s Johnson Space Center, world-class universities, a premier commercial space industry, major military installations, and an unmatched aerospace workforce give Texas every asset the United States Space Academy requires,” the governor added.