Unique cell therapy developed in Houston doses inaugural patient

cancer-fighting innovation

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

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.”

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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.

Houston researchers are hard at work in the lab to progress medical advancements at the bedside. Getty Images

These 3 medical innovations are ones to watch in Houston

Research roundup

Every day, important research is being completed under the roofs of Houston medical institutions. From immunotherapy to complex studies on how a memory is made, Houston researchers are discovering and analyzing important aspects of the future of medicine.

Here are three research projects currently being conducted around town.

University of Houston's potential solution to sickle cell disease

Vassiliy Lubchenko is a University of Houston associate professor of chemistry. Courtesy of UH

For the most part, sickle cells have been a mystery to scientists, but one University of Houston professor has recently reported a new finding on how sickle cells are formed — enlightening the medical community with hopes that better understanding the disease may lead to prevention.

Vassiliy Lubchenko, UH associate professor of chemistry, shared his new finding in Nature Communications. He reports that "droplets of liquid, enriched in hemoglobin, form clusters inside some red blood cells when two hemoglobin molecules form a bond — but only briefly, for one thousandth of a second or so," reads a release from UH.

In sickle cell disease, or anemia, red blood cells are crescent shaped and don't flow as easily through narrow blood vessels. The misshapen cells are caused by abnormal hemoglobin molecules that line up into stiff filaments inside red blood cells. Those filaments grow when the protein forms tiny droplets called mesoscopic.

"Though relatively small in number, the mesoscopic clusters pack a punch," says Lubchenko in the release. "They serve as essential nucleation, or growth, centers for things like sickle cell anemia fibers or protein crystals. The sickle cell fibers are the cause of a debilitating and painful disease, while making protein crystals remains to this day the most important tool for structural biologists."

Lubchenko conclusion is that the key to prevent sickle cell disease is to is to stop the formation of the initial clusters so fibers aren't able to grow out of them.

Baylor College of Medicine's immunotherapy research in breast cancer

science-Digital Composite Image Of Male Scientist Experimenting In Laboratory

Baylor College of Medicine researchers are looking into the complexities of immune cells in breast cancer. Getty Images

Baylor College of Medicine researchers are leading an initiative to figure out the potential effect of immunotherapy on different types of breast cancers. Their report is featured in Nature Cell Biology.

The scientists zoned in on two types of immune cells — neutrophils and macrophages — and they found frequency differed in a way that indicated potential roles in immunotherapy.

"Focusing on neutrophils and macrophages, we investigated whether different tumors had the same immune cell composition and whether seemingly similar immune components played the same role in tumor growth. Importantly, we wanted to find out whether differences in immune cell composition contributed to the tumors' responses to immunotherapy," says Dr. Xiang 'Shawn' Zhang, professor at the Lester and Sue Smith Breast Center and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, in a news release.

Further exploring the discrepancies between the immune cells and the role they play in tumor growth will help better understand immunotherapy's potential in certain types of breast cancer.

"These findings are just the beginning. They highlight the need to investigate these two cellular types deeper. Under the name 'macrophages' there are many different cellular subtypes and the same stands for neutrophils," Zhang says. "We need to identify at single cell level which subtypes favor and which ones disrupt tumor growth taking also into consideration tumor heterogeneity as both are relevant to therapy."

Rice University, UTHeath, and UH's memory-making study

Researchers from all corners of Houston are diving into how memories are made. Courtesy of Rice University

When you make a memory, your brain cells structurally change. Through a multi-institutional study with researchers from UH, Rice University, and the University of Texas Health Science Center at Houston, we now know more about the way memories are made.

When forming memories, three moving parts work together in the human brain — a binding protein, a structural protein and calcium — to allow for electrical signals to enter neural cells and change the molecular structures in cognition. The scientists compared notes on how on that binding protein works.

The team's study was published in the Proceedings of the National Academy of Sciences. Peter Wolynes, a theoretical physicist at Rice, UH physicist Margaret Cheung, and UTHealth neurobiologist Neal Waxham worked together to understand the complex process memories experience in the process of being made.

"This is one of the most interesting problems in neuroscience: How do short-term chemical changes lead to something long term, like memory?" Waxham says in a release from Rice. "I think one of the most interesting contributions we make is to capture how the system takes changes that happen in milliseconds to seconds and builds something that can outlive the initial signal."

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Axiom Space announces new CEO amid strategic leadership change

new leader

Six months after promoting Tejpaul Bhatia from chief revenue officer to CEO, commercial space infrastructure and human spaceflight services provider Axiom Space has replaced him.

On Oct. 15, Houston-based Axiom announced Jonathan Cirtain has succeeded Bhatia as CEO. Bhatia joined Axiom in 2021. Cirtain remains the company’s president, a role he assumed in June, according to his LinkedIn profile.

In a news release, Axiom said Cirtain’s appointment as CEO is a “strategic leadership change” aimed at advancing the company’s development of space infrastructure.

Axiom hired Cirtain as president in June, according to his LinkedIn profile. The company didn’t publicly announce that move.

Kam Ghaffarian, co-founder and executive chairman of Axiom, said Cirtain’s “proven track record of leadership and commitment to excellence align perfectly with our mission of building era-defining space infrastructure that will drive exploration and fuel the global space economy.”

Aside from praising Cirtain, Ghaffarian expressed his “sincere gratitude” for Bhatia’s work at Axiom, including his leadership as CEO during “a significant transition period.”

Bhatia was promoted to CEO in April after helping Axiom gain more than $1 billion in contracts, Space News reported. He succeeded Ghaffarian as CEO. Axiom didn’t indicate whether Bhatia quit or was terminated.

Cirtain, an astrophysicist, was a senior executive at BWX Technologies, a supplier of nuclear components and fuel, for eight years before joining Axiom. Earlier, Cirtain spent nearly nine years in various roles at NASA’s Marshall Space Flight Center in Huntsville, Alabama. He previously co-founded a machine learning company specializing in Earth observation.

“Axiom Space is pioneering the commercialization of low-Earth orbit infrastructure while accelerating advancements in human spaceflight technologies,” Cirtain said. “I look forward to continuing our team’s important work of driving innovation to support expanded access to space and off-planet capabilities that will underpin the future of space exploration.”

Among other projects, Axiom is developing the world’s first commercial space station, creating next-generation spacesuits for astronauts and sending astronauts on low-Earth orbit missions.

Houston billionaire benefactors will donate almost entire fortune to charity

Giving Back

Houston billionaires Rich and Nancy Kinder plan to donate an astounding 95% of their multi-billion-dollar wealth to charities, they told ABC13's Melanie Lawson.

The news comes as the Kinder Foundation announced an $18.5 million expansion project for Emancipation Park in the heart of Third Ward. That historic park was founded by slaves in 1872.

The Kinders are one of the wealthiest couples in the nation, worth $11.4 billion, according to Forbes. You've certainly seen the Kinder name on buildings and facilities around the city of Houston.

The Kinders are also among the most generous, giving away hundreds of millions to Houston institutions and charities. Their plan is to give away almost all of their wealth, or more than $10 billion.

Rich Kinder helped build oil and gas pipeline giant Kinder Morgan, but he stepped down as CEO more than a decade ago for a what he calls a bigger cause.

"Well, I think we'd all like to leave the world a little better place than we found it," he said. "And we just felt early on that the right thing to do was to try to give most or all of that away. So that's what we plan to do during our lifetime and after our death."

They found kindred spirits as one of the first couples to sign The Giving Pledge, established by billionaires Bill and Melinda Gates and Warren Buffett.

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Continue reading the full story, with video, on ABC13.com.

Mark Cuban calls AI ‘the greater democratizer’ for young entrepreneurs

eyes on AI

Texas billionaire Mark Cuban—whose investment portfolio includes Houston-based Holliball, a startup that makes and sells large inflatable holiday ornaments—believes AI is leveling the playing field for budding low-income entrepreneurs.

At the recent Clover x Shark Tank Summit in Las Vegas, the Shark Tank alum called AI “the greater democratizer.”

Cuban told Axios that free and low-cost AI tools enable disadvantaged teenagers to compete with seasoned professionals.

“Right now, if you’re a 14- to 18-year-old and you’re in not-so-good circumstances, you have access to the best professors and the best consultants,” Cuban said. “It allows people who otherwise would not have access to any resources to have access to the best resources in real time. You can compete with anybody.”

While Cuban believes AI is “the great democratizer” for low-income young people, low-income workers still face hurdles in navigating the AI landscape, according to Public Works Partners, an urban planning and consulting firm. The firm says access to AI among low-income workers may be limited due to cost, insufficient digital literacy and infrastructure gaps.

“Without adequate resources and training, these workers may struggle to adapt to AI-driven workplaces or access the educational opportunities necessary to acquire new skills,” Public Works Partners said.

Texas 2036, a public policy organization focused on the state’s future, reported in January AI jobs in Texas are projected to grow 27 percent over the next decade. The number 2036 refers to the year when Texas will celebrate its bicentennial.

As for the current state of AI, Cuban said he doesn’t think the economy is witnessing an AI bubble comparable to the dot-com bubble, which lasted from 1998 to 2000.

“The difference is, the improvement in technology basically slowed to a trickle,” Cuban said of the dot-com era. “We’re nowhere near the improvement in technology slowing to a trickle in AI.”

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