Engineering CAR T Cells to Deliver Endogenous RNA Wakes Solid Tumors to Respond to Therapy

PHILADELPHIA—Chimeric antigen receptor (CAR) T cell therapy, which uses engineered T cells to treat certain types of cancers, has often been a challenging approach to treating solid tumors. CAR T cells need to recognize a specific target on cancer cells to kill them. However, cancer cells do not always have the target, or they find ways to hide the target and stay invisible to CAR T cell attack. A new study from Penn Medicine, published online in Cell, demonstrates that RN7SL1, a naturally occurring RNA, can activate the body’s own natural T cells to seek out the cancer cells that have escaped recognition by CAR T cells. This may help improve efforts to treat solid tumors, which represent most human cancers.

“CAR T cells typically are like lone soldiers without backup. However, if given the right tools, they can kickstart the body’s own immune system and give them help against the cancer cells missed with CAR T cells alone,” said co-lead author Andy J. Minn, MD, PhD, a professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania and director of the Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation at Penn.

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Cancer therapy breakthrough in vitro using self-assembled drugs

ONE of the most challenging aspects of cancer treatment is the huge variety of different tumours that can occur with each one potentially requiring a different solution because unfortunately, one drug does NOT fit all.

In addition, another major issue of many current drugs is their poor selectivity towards cancers resulting in problems such as normal tissue toxicity, severe side effects and the development of drug resistance.

Now, a team of scientists at the University of Huddersfield is researching how to combat these challenges by using “self-assembled” drugs and although the research is in its very early stages, they’ve already had a breakthrough.

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This nanoscopic tool could help doctors detect cancer in a routine urine test

By Wale Azeez  

Researchers at the Massachusetts Institute of Technology (MIT) have created a nanoparticle diagnostic tool that can detect cancer cells in urine.

The tool, invisible to the naked eye at less than 100 nanometres wide, could also be modified to work as an imaging agent to highlight a confirmed cancerous tumour’s location from a scan.

According to the researchers, the nanoparticle tool, once approved for human use, could be incorporated into routine medical urine tests to screen for traces of cancer cells.

If cancer is found, the patient could be given the nanoparticle to ingest before undergoing a Positron Emission Tomography (PET) imaging scan to find the source of the disease.

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Radio-wave Therapy Is Safe for Liver Cancer Patients and Shows Improvement in Overall Survival

Newswise — Researchers at Wake Forest School of Medicine have shown that a targeted therapy using non-thermal radio waves is safe to use in the treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer. The therapy also showed a benefit in overall survival.

The study findings appear online in 4Open, a journal published by EDP Sciences.

“HCC accounts for nearly 90% of all liver cancers, and current survival rates are between six and 20 months,” said Boris Pasche, M.D., Ph.D., chair of cancer biology and director of Wake Forest Baptist’s Comprehensive Cancer Center. “Currently, there are limited treatment options for patients with this advanced liver cancer.”

For the study researchers used a device called TheraBionic P1, invented by Pasche and Alexandre Barbault of TheraBionic GmbH in Ettlingen, Germany, that works by delivering cancer-specific, amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) programmed specifically for HCC. 

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Japan launches new cancer treatment using special antibodies and beams of light

Hisataka Kobayashi (right), senior investigator at the U.S. National Institutes of Health, shakes hands with Rakuten Group Inc. Chairman and Chief Executive Officer Hiroshi Mikitani

A new cancer treatment that uses light to target and kill only cancer cells, and is believed to have few side effects, has entered into use in Japan, in a world first.

In the treatment, called photoimmunotherapy, antibodies that bind only to cancer cells are administered to patients.

Harmless by themselves, the antibodies, when illuminated for several minutes with near-infrared lasers, trigger a chemical reaction that “destroy only cancer cells with pinpoint accuracy,” according to Hisataka Kobayashi, senior investigator at the U.S. National Institutes of Health, who developed the method.

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BioNTech Now Aims Its mRNA Technology at Cancer

Following its success against COVID-19, BioNTech is now focused on its cancer vaccines.

By  Ameya Paleja

Buoyed by the success of its mRNA technology against COVID-19, BioNTech is now focused on its cancer vaccines. The company recently began dosing patients for its Phase II trial for an advanced melanoma vaccine in the European Union.

BioNTech calls itself a “next-generation immunotherapy company pioneering in therapies for cancer and other serious diseases.” The COVID-19 vaccine was a minor detour for the company. The company’s product pipeline is filled with mRNA vaccines targeting different types of cancers, most of which are in preclinical stages. BioNTech recently began the Phase II trial of BNT111, which will test its mRNA vaccine in combination with an antibody-drug, Libtayo, in patients with anti-PD1-relapsed Stage III/ IV melanoma. Libtayo is the commercial name for cemiplimab, co-developed by Regeneron and Sanofi, and is an anti-PD-1 monoclonal antibody.

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DNA-BASED CANCER VACCINE TRIGGERS IMMUNE ATTACK ON TUMORS

BY JIM GOODWIN-WUSTL

“We think this is the first report of the use of a neoantigen DNA vaccine in a human, and our monitoring confirms the vaccine was successful in prompting an immune response that targeted specific neoantigens in the patient’s tumor,” William Gillanders says.

Researchers have shown that personalized cancer vaccines made using DNA can program the immune system to attack malignant tumors, including breast and pancreatic cancers.

The researchers conducted the study in mice with breast cancer and one patient with late-stage pancreatic cancer.

The COVID-19 vaccines—designed using bits of genetic information that prime our immune systems to recognize and fight off viral infections—have become lifesavers in the global fight to end the pandemic.

Now, the new research has shown that a similar vaccine approach can be used to create personalized vaccines that program the immune system to attack malignant tumors, including breast and pancreatic cancers.

The tailor-made vaccines are designed to target mutated proteins called neoantigens that are unique to a patient’s tumors. Unlike the COVID-19 vaccines made by Moderna and Pfizer/BioNTech that rely on genetic material called mRNA, the personalized cancer vaccines are made using DNA.

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Innovative technique developed to destroy cancerous kidney cells

Figure 1 Cathepsin S (CS) protein expression levels are induced through the -1048 promoter fragment from the CTTS gene upon Paclitaxel or hydrogen peroxide stimulation. HEK293 and 769P cells were stimulated with increasing doses of Paclitaxel (Pac) and hydrogen peroxide (HP) and soluble lysates prepared after 24 h and equal volumes analyzed by Western blotting for cathepsin S (CS), BAX and actin expression (Panel A). Similarly, total RNA was isolated from cells stimulated for 24 h with increasing doses of Pac or HP and equal quantities of template cDNA analyzed for transcriptional expression of CS, BAX and Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH, Panel B). Promoter fragments, derived from the transcriptional start site of the CTTS gene to -1048 and -564, were PCR cloned and fused to a promoter-less GFP encoding plasmid (Panel C) and evaluated for GFP expression in equal volumes of HEK293 and 769P cleared whole cell lysates (WCLs) under Pac (10 μg/mL and 5 μg/mL, respectively) or HP (5 μM) stimulatory conditions. GFP expression was also quantified, standardized and corrected against GFP expression from cells stimulated with carrier alone and is shown as a fold change over basal GFP expression (Panel D). HEK293 cells transfected with pCS-1048 or pCS-564 and stimulated with Pac (5 μg/mL) for 24 h were also fixed and visualized for GFP expression using laser scanning confocal microscopy (Panel E). The red bar indicates 1 micron. Quantified data are presented as the mean ± SEM and its significance (where p < 0.05) determined, using a two-way Student’s t-test (* p < 0.05, ** p < 0.01 and *** p < 0.001).

An innovative new technique that encourages cancer cells in the kidneys to self-destruct could revolutionize the treatment of the disease, a new study in the journal Pharmaceutics reports.

During this unique study, researchers from the University of Surrey and Sechenov First Moscow State Medical Universityin Russia investigatedwhethercertain naturally occurring proteins within the body can be used treat cancer.

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HARVARD SCIENTISTS EXCITED BY RESULTS ON NEW CANCER VACCINE

A RECENT STUDY OF PERSONALIZED CANCER VACCINES SHOWED “VERY REWARDING” RESULTS.

By VICTOR TANGERMANN

A team of researchers say they’ve designed a personalized cancer vaccine capable of inducing an immune response that fights off melanoma, the deadliest form of skin cancer, that lasts for several years.

In a study published in the journal Nature Medicine back in January, the scientists examined eight subjects who previously had their melanoma surgically removed, but were still at a high risk of recurrence.

All eight were injected with the experimental vaccine called NeoVax. The results were promising: the researchers found a vaccine-induced immune response in all patients that can “persist over years,” according to the paper.

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Engineered Immune Cells Deliver Anticancer Signal, Prevent Cancer From Spreading

By  U.S. National Institutes of Health

Scientists have genetically engineered immune cells, called myeloid cells, to precisely deliver an anticancer signal to organs where cancer may spread. In a study of mice, treatment with the engineered cells shrank tumors and prevented the cancer from spreading to other parts of the body. The study, led by scientists at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health, was published March 24, 2021, in Cell.

“This is a novel approach to immunotherapy that appears to have promise as a potential treatment for metastatic cancer,” said the study’s leader, Rosandra Kaplan, M.D., of NCI’s Center for Cancer Research.

Metastatic cancer — cancer that has spread from its original location to other parts of the body — is notoriously difficult to treat. Dr. Kaplan’s team has been exploring another approach: Preventing cancer from spreading in the first place.

Before cancer spreads, it sends out signals that get distant sites ready for the cancer’s arrival — like calling ahead to have the pillows fluffed in your hotel room prior to arrival. These “primed and ready” sites, discovered by Dr. Kaplan in 2005, are called premetastatic niches.

In the new study, the NCI team explored the behavior of immune cells in the premetastatic niche. Because Dr. Kaplan is a pediatric oncologist, the team mainly studied mice implanted with rhabdomyosarcoma, a type of cancer that develops in the muscles of children and often spreads to their lungs.

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TINY ROBOTS CAN NOW SMUGGLE DRUGS INTO BRAIN TUMORS

The future of cancer treatment may be robot-delivered.

By Jay Sprogell

THE FUTURE OF MEDICINE is going to be hand-delivered — but not by mail carriers. Instead, life-saving drugs will be parceled, smuggled, and transported in the body via tiny, self-propelled microbots.

In a study published Wednesday in the journal Science Robotics, a research team in China designed a new kind of bio-hybrid microbot that uses clever biological disguises to get even closer to the source of disease in the body in order to provide the most targeted (and effective) treatment.

The target of choice? Hard to treat illness epicenters like brain tumors.

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