Natural Killer Cells, Primed with an Antibody, Induce Remissions in Patients with Advanced Lymphoma

Two patients with advanced Hodgkin lymphoma were told their tumors were
so resistant to treatment that hospice was their best option. Then, they were
enrolled in a clinical trial of a novel immunotherapy involving so-called
natural killer cells. After treatment, they saw complete remission.
Researchers say the results are a hopeful if preliminary sign of the potential of immunotherapies harnessing natural killer, or NK, cellsinnate immune system cells that have certain advantages over the more commonly recognized adaptive T cell cancer therapies.
The treatment in the study, developed by the University of Texas MD Anderson Cancer Center and the German drug maker Affimed, combined offthe-shelf NK cells with a separate antibody that primes the cells to recognize a specific protein signature of the tumors. Two additional patients administered
the same treatment have shown ongoing partial responses.

These results show you just how powerful NK cells are,” said Katy Rezvani,
a stem-cell transplant physician and NK cell researcher at MD Anderson, who
is spearheading the development of this new treatment.
It’s amazing when you see these responses for patients who have so few
options, patients who’ve been told that they should go to hospice,” Rezvani
said.“I cannot begin to tell you how satisfying this is for clinicians.
Data from the study is to be presented at the annual meeting of the American
Association for Cancer Research (AACR).
Source: https://www.mdanderson.org/
AND
https://www.mskcc.org/

Scientists Have Possibly Cured HIV

An American research team reported that it has possibly cured HIV in a woman for the first time. Building on past successes, as well as failures, in the HIV-cure research field, these scientists used a cutting-edge stem cell transplant method that they expect will expand the pool of people who could receive similar treatment to several dozen annually.

Their patient stepped into a rarified club that includes three men whom scientists have cured, or very likely cured, of HIV. Researchers also know of two women whose own immune systems have, quite extraordinarily, apparently vanquished the virus. Carl Dieffenbach, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, one of multiple divisions of the National Institutes of Health that funds the research network behind the new case study, told NBC News that the accumulation of repeated apparent triumphs in curing HIV “continues to provide hope.”

It’s important that there continues to be success along this line,” he said.

In the first case of what was ultimately deemed a successful HIV cure, investigators treated the American Timothy Ray Brown for acute myeloid leukemia, or AML. He received a stem cell transplant from a donor who had a rare genetic abnormality that grants the immune cells that HIV targets natural resistance to the virus. The strategy in Brown’s case, which was first made public in 2008, has since apparently cured HIV in two other people. But it has also failed in a string of others. This therapeutic process is meant to replace an individual’s immune system with another person’s, treating their cancer while also curing their HIV. First, physicians must destroy the original immune system with chemotherapy and sometimes irradiation. The hope is that this also destroys as many immune cells as possible that still quietly harbor HIV despite effective antiretroviral treatment. Then, provided the transplanted HIV-resistant stem cells engraft properly, new viral copies that might emerge from any remaining infected cells will be unable to infect any other immune cells.

Source: https://www.nbcnews.com/

Rejuvenation by Controlled Reprogramming

On 19 January 2022, co-founders Rick Klausner and Hans Bishop publicly launched an aging research initiative called Altos Labs, with $3 billion in initial investment from backers including tech investor Yuri Milner and Amazon founder Jeff Bezos. This is the latest in a recent surge of investment in ventures seeking to build anti-aging interventions on the back of basic research programs looking at epigenetic reprogramming. In December, cryptocurrency company Coinbase’s cofounder Brian Armstrong and venture capitalist Blake Byers founded NewLimit, an aging-focused biotech backed by an initial $105 million investment, with the University of California, San Francisco’s Alex Marson and Stanford’s Mark Davis as advisors.

The discovery of the Yamanaka factors’ — four transcription factors (Oct3/4, Sox2, c-Myc and Klf4) that can reprogram a differentiated somatic cell into a pluripotent embryonic-like state — earned Kyoto University researcher Shinya Yamanaka a share of the Nobel prize in 2012. The finding, described in 2006, transformed stem cell research by providing a new source of embryonic stem cell (ESC)-like cells, induced pluripotent stem cell (iPSCs), that do not require human embryos for their derivation. But in recent years, Yamanaka factors have also become the focus for another burgeoning area: aging research.

So-called partial reprogramming consists in applying Yamanaka factors to cells for long enough to roll back cellular aging and repair tissues but without returning to pluripotency. Several groups, including those headed by Stanford University’s Vittorio Sebastiano, the Salk Institute’s Juan Carlos Izpisúa Belmonte and Harvard Medical School’s David Sinclair, have shown that partial reprogramming can dramatically reverse age-related phenotypes in the eye, muscle and other tissues in cultured mammalian cells and even rodent models by countering epigenetic changes associated with aging. These results have spurred interest in translating insights from animal models into anti-aging interventions. “This is a pursuit that has now become a race,” says Daniel Ives, CEO and founder of Cambridge, UK-based Shift Bioscience.

The Yamanaka factors that can reprogram cells into their embryonic-like state are at the heart of longevity research

We’re investing in this area [because] it is one of the few interventions we know of that can restore youthful function in a diverse set of cell types,” explains Jacob Kimmel, a principal investigator at Alphabet subsidiary Calico Life Sciences in South San Francisco, California. The zeal is shared by Joan Mannick, head of R&D at Life Biosciences, who says partial reprogramming could be potentially “transformative” when it comes to treating or even preventing age-related diseases. Life Biosciences, a startup co-founded by David Sinclair, is exploring the regenerative capacity of three Yamanaka factors (Oct4, Sox2 and Klf4).

Source: https://www.nature.com/

The Science Of BioPrinting a Human Heart

A company called Biolife4D has developed the technology to print human cardiac tissue by collecting blood cells from a patient and converting these cells to a type of stem cell called Induced Pluripotent Stem (iPS) cells. The technology could eventually be used to create thousands of much-needed hearts for transplantation.

What we’re working on is literally bioprinting a human heart viable for transplantation out of a patient’s own cells, so that we’re not only addressing the problem with the lack of [organ] supply, but by bioengineering the heart out of their own cells, we’re eliminating the rejection,Biolife4D CEO Steven Morris said during an appearance on Digital Trends Live, referring to the body’s impulse to reject a transplanted organ.

It starts with a patient’s own cells and ends with a 3D bioprinted heart that’s a precise fit and genetic match. The BIOLIFE4D bioprinted organ replacement process begins with a magnetic resonance imaging (MRI) procedure used to create a detailed three-dimensional image of a patient’s heart. Using this image, a computer software program will construct a digital model of a new heart for the patient, matching the shape and size of the original.

A “bio-ink” is created using the specialized heart cells combined with nutrients and other materials that will help the cells survive the bioprinting processHearts created through the BIOLIFE4D bioprinting process start with a patient’s own cells. Doctors safely take cells from the patient via a blood sample, and leveraging recent stem cell research breakthroughs, BIOLIFE4D plans to reprogram those blood cells and convert them to create specialized heart cells.

Bioprinting is done with a 3D bioprinter that is fed the dimensions obtained from the MRI. After printing, the heart is then matured in a bioreactor, conditioned to make it stronger and readied for patient transplant.

Source: https://biolife4d.com/

Breakthroughs In Anti-Aging Research In Near Future

People 50 and older have a lot to look forward to, according to Juvenescence’s Greg Bailey—mainly that we won’t be aging as fast or poorly as our parents. “Science fiction has become science,” said the UK-based anti-aging biotech’s CEO about the company’s completing its $100 million Series B round of financing last week. “I think the world is going to be shocked,” he said in an interview. In total, Juvenescence has now raised $165 million in just 18 months to fund longevity projects with the lofty goal of extending human lifespans to 150 years. Bailey said the money will allow the company “to progress all of our products.” And there’s quite a list of potential therapies.

We have 12 programs based on hard, rigorous science, to try to modify aging. From stem cell research to senolytics to modifying or preventing Alzheimer’s and Parkinson’s diseases,” he said. It’s no secret that anti-aging is big business. According to Endpoints News, “Bank of America has forecast the market will balloon to $610 billion by 2025, from an estimated $110 billion currently.”  “I think there’s a huge amount of skepticism. There’s an enormous number of charlatans…I understand why they would be thinking you know, is this real?” Bailey told Endpoints. “Walk into your local drugstore, you’re going to see about 50 products that claim to be anti-aging, and I can assure you that none of them are.

Bailey said creams that claim everything and do nothing and vitamins that basically give users “expensive urine” are the reason for that skepticism. And investors are not as quick to step up as he would like. Bailey told Endpoints: “We’re dramatically being underserved…it’s not getting the exposure that tech gets, considering the size of the market.” He said he believes there is “a disconnect” on how investors and institutions are viewing anti-aging technology. “I don’t think they quite grasp how fast this is going to happen, and how big it’s going to be.”

Source: https://www.forbes.com/

How To Turn Breast Cancer Cells Into Fat to Stop Them From Spreading

Researchers have been able to coax human breast cancer cells to turn into fat cells in a new proof-of-concept study in mice. To achieve this feat, the team exploited a weird pathway that metastasising cancer cells have; their results are just a first step, but it’s a truly promising approach. When you cut your finger, or when a foetus grows organs, the epithelium cells begin to look less like themselves, and more ‘fluid’ – changing into a type of stem cell called a mesenchyme and then reforming into whatever cells the body needs.

This process is called epithelial-mesenchymal transition (EMT) and it’s been known for a while that cancer can use both this one and the opposite pathway called MET (mesenchymal‐to‐epithelial transition), to spread throughout the body and metastasise. The researchers took mice implanted with an aggressive form of human breast cancer, and treated them with both a diabetic drug called rosiglitazone and a cancer treatment called trametinib. Thanks to these drugs, when cancer cells used one of the above-mentioned transition pathways, instead of spreading they changed from cancer into fat cells – a process called adipogenesis.

The image  shows this process, with the cancer cells tagged with a green fluorescent protein and normal red fat cell on the left. The cancer-turned-fat cells display as brown (on the right) because the red of the fat cells combines with the green of the protein cancer cell tag.

The models used in this study have allowed the evaluation of disseminating cancer cell adipogenesis in the immediate tumour surroundings,” the team wrote in their paper, published in January 2019. “The results indicate that in a patient-relevant setting combined therapy with rosiglitazone and trametinib specifically targets cancer cells with increased plasticity and induces their adipogenesis.

Although not every cancer cell changed into a fat cell, the ones that underwent adipogenesis didn’t change back. “The breast cancer cells that underwent an EMT not only differentiated into fat cells, but also completely stopped proliferating,” said senior author Gerhard Christofori, a biochemist at the University of Basel, in Switzerland. “As far as we can tell from long-term culture experiments, the cancer cells-turned-fat cells remain fat cells and do not revert back to breast cancer cells.

So how does this work? Well, as a drug trametinib both increases the transition process of cells – such as cancer cells turning into stem cells – and then increases the conversion of those stem cells into fat cellsRosiglitazone was less important, but in combination with trametinib, it also helped the stem cells convert into fat cells. “Adipogenic differentiation therapy with a combination of rosiglitazone and [trametinib] efficiently inhibits cancer cell invasion, dissemination, and metastasis formation in various preclinical mouse models of breast cancer,” wrote the team.

Source: https://www.cell.com/
AND
https://www.sciencealert.com/