Keeping the physical appointment was critical, the show of support appreciated by Renville County Commissioner – West Central Tribune

When he called the Olivia Hospital and Clinic to postpone his physical, he was urged to keep it. Physicals are important, he was reminded.

Keeping that date proved to be a lifesaving decision.

The physical went well, and shortly after he told his daughter that he was as fit as a horse.

But Dr. Jon Kemp, his primary physician who had urged him to keep the date for the physical, noticed a slight abnormality in a standard blood test. He recommended further testing.

On Dec. 20 Kramer was diagnosed with multiple myeloma.

Thanks to the early diagnosis, Kramer, age 62, has the means of keeping this disease at bay. Its a cancer of the plasma cells in bone marrow, and is the second most common blood cancer.

He is about to undergo a stem cell transplant this week as part of his treatment.

He learned that hes not alone on the journey ahead.

At Tuesdays meeting of the Renville County Board of Commissioners, fellow board members came wearing T-shirts proclaiming: In this county, nobody fights alone.

Organizers of the surprise sold 76 of the T-shirts to show support for Kramer and raise funds for the Renville County Walk in the Park campaign. More than 40 T-shirt wearing supporters joined the meeting via Zoom. Staff in the health department sang a song to express their support, and staff members told him they would keep him in their thoughts and prayers.

Thank you, said Kramer. He told the West Central Tribune that he was totally surprised by the display of support.

He has lots of support from family and friends, and its all-important. Kramer farms in eastern Renville County. He has lined up plenty of helping hands while he undergoes the stem cell transplant, which will sideline him for at least six weeks.

He said doctors are confident the stem cell transplant can knock the cancer into remission. They will be harvesting bone marrow cells and freezing a portion of them to make it possible to perform at least two more transplants in future years as well.

The decision to keep the date of that routine physical made all the difference. Absolutely, said Kramer.

Health providers told him that in too many cases, multiple myeloma is not diagnosed until a patient comes in with a broken leg or other bone, and wondering why. The cancer carves holes and weakens bones as it progresses unbeknownst to the person.

Thanks to the early diagnosis, Kramer said they found only pinholes in his bones, having caught the disease in the first of its three stages. He began chemotherapy in early January, and it has proven effective, he added.

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Keeping the physical appointment was critical, the show of support appreciated by Renville County Commissioner - West Central Tribune

Appia Bio aims for a new kind of off-the-shelf CAR-T with $52M raise – FierceBiotech

Nobel Prizewinner David Baltimore, Ph.D.has always dreamed of turning Los Angeles into a biotech hub. He tried to help it along as president of the California Institute of Technology some 20 years ago, but the idea didnt seem to stick. Now, hes getting another crack at it with a new cancer cell therapy company co-founded with a group of Caltech and Kite Pharma alums.

Appia Bio launches with $52 million to develop off-the-shelf cell therapies for cancer based on hematopoietic, or blood-forming, stem cells. Its platform, dubbed ACUA, allows the programming of stem cells to become invariant natural killer T (iNKT) cells, a powerful subtype of T cell that some folks think of as a hybrid between a natural killer (NK) cell and a T cell, said JeenJoo JJ Kang, Ph.D., CEO of Appia Bio.

Though everybody has iNKT cells in their body, these cells are exceedingly rare. They make up just a fraction of white blood cells found in the peripheral blood, so its hard to produce them in the traditional way, which is to draw blood and expand those cells, Kang said.

[iNKT] cells have multiple tumor cell-killing mechanisms through the natural killer and T cell pathway, she added. Were going to engineer them with a CAR and we think that is positive because it can address more heterogeneous tumor antigen presentations and get around antigen loss.

RELATED: Harper, Seidenberg's Westlake Village BioPartners reels in $500M across 2 funds

Antigen loss or antigen escape is a process in which cancer cells stop expressing the antigen the CAR-T is designed to hunt down, such as CD19. Targeting more than one antigen could disrupt that escape mechanism and prevent relapse. It could also improve the odds of cell therapy working in solid tumorsa major pain point.

Besides solving these problems, Appia also hopes to address the barrier of access. Autologous cell therapiesthat is, those made from a patients own cellsare complex, expensive and time-consuming to make. Some patients dont have enough T cells or T cells of good enough quality to make those treatments.

Producing large amounts of iNKT cells from stem cells that can be stored until theyre needed could make cell therapy available to more patients and at a lower cost.

Being able to mass-produce a cell therapy product that can be dosed to thousands of patients out of a single manufacturing run can significantly affect the economics of what the viable price point is, Kang said. That is another aspect that is a part of our goals: to bring that price down.

RELATED: Catamaran Bio sets sail with $42M to create off-the-shelf CAR-NK treatments

The ACUA technology is based on research out of the laboratory of co-founder Lili Yang, Ph.D., an associate professor at the University of California, Los Angeles who worked under Baltimore as a student and postdoc at Caltech.

Appias founding team also includes Pin Wang, Ph.D., of the University of Southern California and Kite alums Edmund Kim, Ph.D., and Jeff Wiezorek, M.D. Kim, who led corporate development at Kite, is Appias chief operating officer. Wiezorek,who led cell therapy development at Kite, is Appias chief medical officer.

Gilead acquired Kite in 2017, the same year its first CAR-T therapy, Yescarta, scored FDA approval. Later on, Wiezorek and Kims search for their next project coincided with the maturation of Yangs technology at UCLA.

Bringing the two together made a lot of sense, so we did that, Baltimore said. Kang came on board from The Column Group, the VC shop she joined in 2015 after completing her Ph.D. atyou guessed itCaltech.

RELATED: AACR: A look at next-gen CAR-T therapies for blood cancers

With the series A round in the bank, the team will turn to company building and advancing its lead programs in blood cancers and solid tumors, with plans to be in the clinic by the end of 2023, Kang said. 8VC led the financing, while Two Sigma Ventures, Sherpa Healthcare Partners and Freeflow Ventures also chipped in.

The company is setting up shop in Los Angeles County.

Im overjoyed that were getting space in Culver City and the people that we found really appreciate Los Angeles, Baltimore said. Maybe we can make it a biotech hubwe'll seebut at least we can get this company going."

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Appia Bio aims for a new kind of off-the-shelf CAR-T with $52M raise - FierceBiotech

Experimental treatments risk further medicalisation of menopause – The BMJ

Many women experience debilitating menopause symptoms. Fledgling interventions aimed at delaying menopause or treating symptoms are attracting commercial interest, but robust evidence of potential benefit and harms for patients is lacking. Sally Howard reports

Ovarian tissue cryopreservation and transplantation (OTCT)surgical procedures successfully used to restart ovarian function in young women who have undergone chemotherapy1are being offered to healthy women in the United Kingdom with a view to reinstate their pre-menopausal endocrine function. But robust evidence of effectiveness and safety in this indication is lacking, and some experts see this as overmedicalisation of menopause.

The private Birmingham based clinic Profam charges healthy women between 7000 and 11000 (8000-12500; $9500-$15000) for OTCT. Before menopause, a slice of oocyte rich ovary is laparoscopically resected, cryopreserved, and then regrafted into the pelvis or subcutaneously in the forearm after menopause.

Meanwhile, patients in Canada are being advertised a proposed surgical treatment for early menopause that would involve transferring newly recognised germline stem cells from the ovarian lining to the ovary despite limited knowledge of their development into new oocytes.2 Fertility CARE: The IVF Center, a clinic based in Florida, US, markets the treatment OvaPrime as a means of stopping your biological clock, which is on the cusp of being approved for mainstream use just over the northern border.3

Were seeing something like the commercial big bang that happened with IVF in the 1990s, says Evelyn Telfer, a biologist at the University of Edinburgh who researches the clinical potential of germline oocyte precursor cells. Private IVF clinics have proliferated since the 1990s, and some now sell a plethora of non-evidence based add-on interventions. This risks what we saw with IVFpatients paying a lot of money for treatments not ready to be rolled out, she says.

ProFams cofounder Simon Fishel, an IVF scientist,

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Experimental treatments risk further medicalisation of menopause - The BMJ

Biopreservation Market Know the diverse technological advancements in the biopreservation – BioSpace

Biopreservation is a process for conserving the tissues, organs and cells along with maintaining their integrity and functionality at different temperatures for a prolonged period of time. The necessary products for biopreservation are cryo bags, tubes, refrigerators, liquid nitrogen tanks, and freezers. These biopreservation equipment have applications in stem cell, DNA, and plasma and tissue research which helps the market to grow steadily. Various researches being carried out in cell therapy and the increasing number of bio banks also encourage market expansion. Currently, the geriatric population is affected with many disorders related to their lifestyle, namely cardiovascular disease, chronic illness, hypertension, and cancer. Biopreservation applications such as drug discovery, regenerative medicines, and bio banking help the consumers or patients during their life span and even at the time of death.

The enormous growth in the global biopreservation market is accelerated by the rising healthcare expenditure, increasing trend of conserving cord blood stem cells of newborns, and the growing investments in research and development pertaining to this field. A considerable healthcare spending is expected to drive the gene banks, bio banks and hospitals to focus on biopreservation. High costs of advanced techniques and stability issues such as tissue injury during thawing and freezing have been considered as some of the primary factors restraining the biopreservation market growth. One of the prominent names in the industry, BioLife Solutions has signed a ten years business supply agreement with Bellicum Pharmaceuticals for manufacturing, marketing of proprietary tissue and cell, and various cellular immunotherapies which target solid tumors and blood cancers. The influential regions for the biopreservation market are North America, Europe and Asia Pacific. Asia Pacific is expected to offer significant growth opportunities to market players, mostly driven by the demand arising from India and China.

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Global Biopreservation Market: Overview

Biopreservation involves maintaining the functionality and integrity of cells, tissues, and organs outside their natural environment for an extended period of storage at different temperatures. For instance, vaccines save 3 million lives every year in the U.S, however, vaccines worth US$ 20 million are wasted each year due to inadequate storage and improper refrigeration.

Biopreservation safeguards the stability, purity, and quality of biospecimens saved in hospitals, biobanks, and gene banks. For instance, preservation of red blood cells (RBCs) is required for the ready availability of safe blood for blood transfusion needs. The biopreservation of RBCs for clinical purposes can be divided on the basis of techniques used to attain biologic stability and safeguard a viable state after extended storage times.

Global Biopreservation Market: Key Trends

The major factors driving the global biopreservation market include increasing R&D expenditure, increasing number of sperm and egg banks, increasing demand for preserving the stem cells of newborns, and rising adoption of regenerative medicine.

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Across the world, the increasing healthcare expenditure for health and well-being will stimulate the growth of the biopreservation market. This is because healthcare expenditure accounts for a significant part of the developmental budget of most countries. According to data from the World Bank, public healthcare spending is expected to rise at a substantially high rate, which along with a substantial healthcare spending will be an important driver for gene banks, hospitals, and biobanks, which are the key end-users of biopreservation market.

A large population afflicted with chronic disorders such as cardiovascular diseases, diabetes, cancer, and hypertension as well as lifestyle diseases will bolster the markets growth. The increasing public and private spending on, medical goods and services, rising disposable income, increasing demand for biobanking services for the preservation of cells, tissues, and organs, and rising disposable income are also expected to further enhance the growth of the global biopreservation market.

Global Biopreservation Market: Market Potential

In a recent development in the biopreservation industry, BioLife Solutions, a leading name in developing, manufacturing, and marketing of proprietary cell and tissue has entered into a ten year business supply agreement with Bellicum Pharmaceuticals. The latter is a leading name in the development of cellular immunotherapies for cancers and inherited blood disorders. On account of this supply agreement, BioLifes CryoStor cell freeze media is incorporated into Bellicums production process for various cellular immunotherapies that targets blood cancers and solid tumors.

In another industry development, BioLife Solutions has entered into a partnership with transportation firm MNX and expects heightened demand for its biologistics services with the entry of more cell therapies into the clinic.

Global Biopreservation Market: Regional Outlook

The global biopreservation market can be analyzed with respect to the regional segments of North America, Europe, Asia Pacific, and Rest of the World. In North America, the U.S. accounts for almost half the revenue of the region. This is due to the increasing demand for detection of chronic diseases, government stipulations for the ethical usage of biological samples, and introduction of newer of biopreservation methodologies.

Asia Pacific biopreservation market, driven by India and China will display a sustainable growth over the next couple of years

Global Biopreservation Market: Competitive Analysis

Some of the key companies operating in the global Biopreservation market include Thermo Fischer Scientific Inc., VWR Corporation, Lifeline Scientific Inc., BioCision LLC, Custom Biogenic Systems Inc., Princeton Cryotech Inc., Sigma-Aldrich Corporation, Biolife Solutions Inc., Cesca Therapeutics Inc., Core Dynamics Ltd., and So-Low Environmental Equipment Co. Inc.

Top companies in the market are focused on mergers and acquisitions, practicing effective services, and develop new products to stay competitive in the biopreservation market. Expanding geographical reach and developing a broad product portfolio with respect to refrigerators, freezers, and consumables is also leading to the increased market share of some of the top players.

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The regional analysis offers market assays across:

The study, prepared through the L.E.A.P mechanism adds a dimension of infallibility and assures precise information on all the growth dynamics.

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Biopreservation Market Know the diverse technological advancements in the biopreservation - BioSpace

Reawakened immune cells attack cells tied to diseases of aging – STAT – STAT

Scientists have started to test whether natural killer, or NK, cells can be trained to go after hard-to-cure blood cancers in human patients. But making these sentinels of the innate immune system a potential boon to human health spans might be simpler: Rather than needing to be genetically engineered or primed with synthetic antibodies, they just need to be turned on.

In mice, researchers reported on Monday in the journal Med, activating NKT cells can eliminate the senescent cells partly responsible for many diseases of aging. If the results hold up, they could offer a promising alternative to senolytics experimental drugs that destroy these zombified cells that pile up and pollute your tissues as you get older. Although dozens of such drugs have postponed or even reversed diseases of aging in mouse experiments, clinical trials have thus far underwhelmed.

Its an interesting approach that works in experimental animals with two different conditions, said geriatrician James Kirkland of the Mayo Clinic, whose discovery that giving old mice senescent cell-crushing compounds makes the animals live longer, healthier lives, helped take senolytics from backwater to boomtown. Were going to need multiple ways of getting at senescent cells, he said. Any step forward is important, and this is quite a nice step forward. But he cautioned that a single senolytic strategy is unlikely to work for all age-related conditions.

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For decades, scientists had largely ignored senescent cells old and arrested in a permanent state of suspended animation dismissing them as a quirk of evolution, a clever way for the body to keep damaged cells from proliferating into cancer. But more recently, Kirkland and other researchers established that senescence is actually a driver of the decrepitude that comes with old age. As cells stop dividing, they dont exactly go dormant. In their zombie-like state, they start spewing a cocktail of toxic molecules that cause inflammation, damage surrounding tissues, and contribute to diseases like osteoarthritis, atherosclerosis, diabetes, and Alzheimers.

That realization spurred the creation of at least two dozen companies developing ways to systematically purge the body of senescent cells. Senolytics attracted this wave of investment because it promises a scintillating and fundamental shift in medicine away from the one-drug-one-target-one-disease paradigm of the last century, toward correcting a root cause behind many of them with a single treatment.

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One of those researchers is the new studys senior author, Anil Bhushan of the University of California, San Francisco. In 2019, his lab traced the progression of type 1 diabetes in mice and human pancreatic cells. They discovered that signatures of senescence preceded the onset of disease. When his team removed the senescent pancreatic cells in mice, their metabolism stabilized and their diabetes symptoms went away.

What Bhushan took away from that study was that senescence didnt just happen when the bodys biological clocks wound down too far. It occurred in acute diseases too. Thered been talk in the field that an immune surveillance system maintained tissue homeostasis, said Bhushan. We postulated that that system was failing in the disease state and gradually failing in aging, so the only time wed see senescent cells is when this system fails.

To test that hypothesis, his team first went looking for clues as to the identity of their indolent immune cells. By comparing the transcriptional profile which genes were turned on and off in senescent pancreatic cells to healthy ones, they uncovered that the senescent ones boosted production of their antigen-presenting machinery. These are the proteins that, if a cell were infected with a pathogen, would shuttle little bits of the bacteria or virus to its surface, displaying them for immune cells to find. Then they cross-referenced those results with an analysis of senescent stem cells that accumulate in the fat tissues of obese mice who are fed a chronic, high-fat diet. Those cells also upregulated antigen-presenting molecules, and one in particular: CD1d. That was the lock, said Bhushan. And once wed found it, the key was then obvious.

Only one kind of immune cell binds to CD1d invariant natural killer T cells, or iNKTs. Comprising less than 1% of all peripheral blood immune cells, iNKTs are rare but critical components of the bodys surveillance system, scanning for infected and defective cells in need of removal. When they find them, iNKTs expel torrents of cytokines, which signal to other immune cells to do the dirty work. Bhushan figured that something was interfering with that process. And though he wasnt sure what it was, he knew there was a way to fix it.

In the early 1990s, Japanese scientists from Kirin Brewerys pharmaceutical research lab, looking for anticancer treatments in the porous bodies of marine sponges collected in the Okinawan sea, purified a lipid compound called -galactosylceramide. And they discovered that when CD1d grabs onto this -GalCer lipid, it turns on iNKTs like crazy in mice.

So Bhushans team shot up some of their diet-induced obese mice with -GalCer. Within days, the levels of senescent cells in the mouse fat tissues had dropped. So did their fasting glucose. Their insulin sensitivity also improved. Their metabolism started to look normal.

To see how generalizable the effect was, they repeated the experiment with mice whose lung tissues had been damaged by a chemotherapy drug a common model for idiopathic pulmonary fibrosis, a serious and incurable human lung disease, and one of the nastier complications of Covid-19. In those mice, -GalCer successfully activated iNKTs, again resulting in the removal of senescent cells. The treated mice had fewer damaged cells, and they also lived longer than the control group.

Finally, Bhushan and his colleagues looked at how well activated iNKT cells could tell senescent human cells from healthy ones when cultured together. After 18 hours, 100% of the senescent cells had been destroyed; the vast majority of healthy cells went unscathed. That could give the iNKT approach a potential advantage over the senolytics drugs already in development.

Most of them are repackaged cancer drugs that work by flipping on senescent cells self-destruct buttons. But because zombie cells share a lot of molecular features with their fully animated counterparts, those drugs run the risk of creating lots of collateral damage. Clinical trials of one such drug, 17-DMAG, were abandoned due to toxic side effects in the kidney and brain. Other groups are trying to solve this by engineering a different kind of immune cell, the CAR-T cell, to become a better anti-aging treatment. But CAR-Ts come with their own dangerous side effects and are expensive to make.

Bhushan is optimistic that by returning the cells best trained to suss out senescent cells to the ranks of active immune duty, both these safety and cost concerns can be ameliorated. We have this built in specificity of the immune cells part of their job is telling senescent cells apart from healthy ones were just helping them do their job, he said.

Its still an open question. But clinical trials to answer it could be underway by the end of next year. Bhushans initial discoveries are now being developed by a biotech startup called Deciduous Therapeutics, which he co-founded in 2018. Deciduous is backed by 8VC, CRV, and Laura Demings Longevity Fund, and has until now, been operating in stealth. CEO and co-founder Robin Mansukhani told STAT that the company has been focusing on developing compounds that can best stimulate human iNKTs, whose receptors are structurally a bit different from those of a mouse. He expects Deciduous to file its first investigational new drug application to start human testing within the next 18 months, likely for a metabolic disease or fibrotic lung disorder.

Investors pumped the brakes on senolytics after one of the biggest and brightest stars of the nascent sector and another Longevity Fund portfolio company, Unity Biotechnology, announced last August that its lead drug candidate had failed to reduce knee pain in patients with osteoarthritis. The experimental drug was immediately and unceremoniously dumped, along with nearly one-third of Unitys staff.

But despite the recent slowdown, Mansukhani remains optimistic. The issue in the field has always been what is the actual immune system process behind senescence clearing?he said. And I feel like weve uncovered that.

Mayos Kirkland cautions that deciphering one chapter of the immune system users manual isnt likely to be the whole story. Senescence can be caused by lots of things aging, yes, but also obesity, chemotherapy drugs, and radiation. There are about 40 to 50 different things that can push a cell into a death spiral, said Kirkland. That makes it really hard to define what a senescent cell is, because its molecular makeup depends on how its senescence was induced.

But the good news, according to Kirkland, is that all the fundamental aging processes mitochondria powering down, oxygen radicals disfiguring DNA, rampant inflammation, the spiral toward senescence appear to be tightly interlinked. Its looking increasingly like if you hit one part of this network of things going on, you affect all the rest, and usually in a positive way, he said.

Kirkland, together with his team at Mayo, have had some success with a cocktail of dasatinib and quercetin. In 2019, they reported positive results from a Phase 1 pilot study of nine diabetic kidney disease patients senescent cells were reduced. A Phase 2 study is now underway. And his team has several more trials for serious conditions, including osteoporosis and Alzheimers disease, in the pipeline. Kirkland serves as a scientific adviser to a new senolytics company called NRTK Biosciences that has yet to receive funding and anti-aging supplement company Elysium Health.

But the real question for the future, said Kirkland, is which interventions can you combine to get an additive, synergistic effect? Something that actually alleviates not just one disease of aging, but many, or even all of them? Figuring out how immune cells interplay with senescence is going to be the start of looking for those combinations.

Thats whats next for Bhushans lab a painstaking process of deleting different antigen-displaying peptides across dozens of types of immune cells, and mapping out the almost infinitely complex network of interactions brewing in the toxic stew surrounding senescent cells.

We know we only have part of the story, Bhushan said. We know we can fix whatever is going wrong with iNKTs, but we still dont know exactly what that is.

Science Writer

Megan Molteni is a science writer for STAT, covering genomic medicine, neuroscience, and reproductive tech.

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Reawakened immune cells attack cells tied to diseases of aging - STAT - STAT