Tag Archives: Cancer therapy

MEDICINE: NEW ‘SMART CELL’ THERAPIES TO TREAT CANCER

Finding medicines that can kill cancer cells while leaving normal tissue unscathed is a Holy Grail of oncology research. In two new papers, scientists at UC San Francisco and Princeton University present complementary strategies to crack this problem with “smart” cell therapies—living medicines that remain inert unless triggered by combinations of proteins that only ever appear together in cancer cells.

Biological aspects of this general approach have been explored for several years in the laboratory of Wendell Lim, PhD, and colleagues in the UCSF Cell Design Initiative and National Cancer Institute– sponsored Center for Synthetic Immunology. But the new work adds a powerful new dimension to this work by combining cutting-edge therapeutic cell engineering with advanced computational methods.

For one paper, published September 23, 2020 in Cell Systems, members of Lim’s lab joined forces with the research group of computer scientist Olga G. Troyanskaya, PhD, of Princeton’s Lewis-Sigler Institute for Integrative Genomics and the Simons Foundation’s Flatiron Institute. Using a machine learning approach, the team analyzed massive databases of thousands of proteins found in both cancer and normal cells. They then combed through millions of possible protein combinations to assemble a catalog of combinations that could be used to precisely target only cancer cells while leaving normal ones alone.

In another paper, published in Science on November 27, 2020, Lim and colleagues then showed how this computationally derived protein data could be put to use to drive the design of effective and highly selective cell therapies for cancer. “Currently, most cancer treatments, including CAR T cells, are told ‘block this,’ or ‘kill this,’” said Lim, also professor and chair of cellular and molecular pharmacology and a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

“We want to increase the nuance and sophistication of the decisions that a therapeutic cell makes.” Over the past decade, chimeric antigen receptor (CAR) T cells have been in the spotlight as a powerful way to treat cancer.

In CAR T cell therapy, immune system cells are taken from a patient’s blood, and manipulated in the laboratory to express a specific receptor that will recognize a very particular marker, or antigen, on cancer cells. While scientists have shown that CAR T cells can be quite effective, and sometimes curative, in blood cancers such as leukemia and lymphoma, so far the method hasn’t worked well in solid tumors, such as cancers of the breast, lung, or liver.

Cells in these solid cancers often share antigens with normal cells found in other tissues, which poses the risk that CAR T cells could have off-target effects by targeting healthy organs. Also, solid tumors also often create suppressive microenvironments that limit the efficacy of CAR T cells. For Lim, cells are akin to molecular computers that can sense their environment and then integrate that information to make decisions. Since solid tumors are more complex than blood cancers, “you have to make a more complex product” to fight them, he said.

THE DOCTORS 101 CHRONIC SYMPTOMS & CONDITIONS 21: PERIPHERAL NEUROPATHY

Peripheral Neuropathy is a common problem, and almost a quarter of the population will eventually suffer from it. It is very common in diabetes and metabolic syndrome, alcoholism, and in cancer therapy.

Even getting older is a risk; almost 10% of individuals 65 years old have some symptoms. There are more than 100 different types of peripheral neuropathy, and often it is just one feature of a primary illness.

Sometimes there is no known cause, such as in 2 of my older friends. I have a diminished vibratory sense in my feet, which causes me no noticeable problem. The longer nerves are more likely to be involved, except for the rare sensory ganglionopathy which is symptomatic of some cancers ( a “paraneoplastic disorder”) , some infections and autoimmune diseases.

When the sensory ganglia are involved, the numbness, tingling or pain can be more central, such as in the face or upper arm. There are 3 types of nerves that can be involved in peripheral neuropathy; Sensory, Motor and autonomic.

The sensory nerves deal with sensations, such as hot, cold, touch, pain, tingling, and numbness. Motor nerve involvement results in weakness or paralysis of an arm, leg or other area under Voluntary control. The autonomic nervous system coordinates activities beyond voluntary control, such as sweating, salivation, food propulsion and heart rate, which can be activated or inhibited.

The symptoms of neuropathy depend upon the type of nerve involved. Balance is a complex ability that can be disturbed by a lack of proper sensory nerve function (Position sense or proprioception) motor weakness, vision or coordination which involve higher centers.

The medical evaluation of peripheral neuropathy begins with a family practitioner or internist who does a detailed history, asking about such things as diet, medications, alcohol consumption, and injuries. Vitamin intake is important, but can be overdone.

Peripheral nerve symptoms can actually be caused by excessive B6, pyridoxine. The upper limit is 100 Mg.. A physical exam checks for weakness, sensory problems, reflexes and balance. Blood tests may reveal diabetic, kidney, liver, thyroid or immune problems problems.

A major disorder associated with neuropathy may be revealed and pursued. If nothing turns up, and the neuropathy is significant, referral may be needed to a neurologist, or other appropriate specialist. Many specialized tests and treatments may be needed.

Even with the best of care, a specific “cure” may not be found. Peripheral neuropathy can often be avoided by a healthy lifestyle.

–Dr. C.

Article on Peripheral Neuropathy