A treatment type that uses patients’ own immune cells to attack cancer looks ready for testing in human clinical trials of advanced colorectal cancer, according to researchers at Thomas Jefferson University in Philadelphia, Pennsylvania United States.
In a study paper published in the journal Cancer Immunology Research, the researchers report how they tested the treatment, which is a type of immunotherapy known as chimeric antigen receptor (CAR) T-cell therapy, in mice that were implanted with human colorectal cancer tumours.
The treatment killed colorectal cancer tumours and prevented them spreading.
Successful completion of this last preclinical stage means that the next step would be a phase I clinical trial in human patients.
The progress is significant because there are few treatment options for colorectal cancer once it has advanced.
“The concept of moving [CAR T-cell] therapy to colorectal cancer is a major breakthrough,” said Dr. Karen Knudsen, who is director of the Sidney Kimmel Cancer Centre at Thomas Jefferson University, “and could address a major unmet clinical need.”
Although colorectal cancer is the “third most common” cancer to affect both men and women in the United States, it is the second main cause of cancer deaths.
Estimates suggest that there were 139,992 new cases of colorectal cancer and 51,651 deaths to the disease in the U.S. in 2014, the latest year for official figures.
As with most cancers, most deaths in colorectal cancer occur in patients with advanced disease, which begins when the primary tumor starts to spread.
The tumour can spread either locally into the neighbouring tissue, or through metastasis, a process in which cells escape the primary tumour and migrate to other parts of the body where they can set up new, secondary tumours.
Not all cancer cells that escape a primary tumour succeed in forming secondary tumours. The process is complex and has many steps — from breaking away to migrating, evading the immune system, and setting up camp — and it can fail at any step.
The cells that eventually succeed may no longer resemble the cells of the primary tumour. This is one of the reasons that metastatic cancer is harder to treat.
CAR T-cell therapy is a type of immunotherapy in which clinicians reprogramme genes in “patients’ own immune cells to attack cancer cells.”
To do this, immune system T cells are taken from the patient, genetically reprogrammed in the laboratory, multiplied to vastly increase their number, and then infused back into the patient.
The reprogramming of T cells restores their ability to find and attack cancer cells that had previously been very successful at suppressing the attacks.
However, in order for the T cells to find and kill only the target cancer cells, there has to be a way to identify them uniquely to the T cells. This is where the genetic reprogramming comes in — it makes the T cell seek out a unique marker, called a tumour antigen, on the cells.
In the case of the new study, the tumour antigen that they used was GUCY2C, whose potential had previously been identified by senior author Adam E. Snook, who is an assistant professor in the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University.
Initially, the scientists tested the therapy on laboratory-cultured cancer cells. They showed that it targeted and killed only those cancer cells that expressed the GUCY2C marker; cancer cells without GUCY2C were spared.
Prof. Snook and colleagues then showed that the CAR T-cell therapy using the GUCY2C tumour antigen successfully treated mice implanted with human colorectal cancer tumours.
All the treated mice survived for the whole of the study’s observation time, which amounted to 75 days. Mice treated with a control therapy survived for an average of 30 days.
In another set of experiments, the researchers used mice that had developed their own “murine” colorectal cancer tumors but that had been genetically altered to “express human GUCY2C.”
When they treated those mice with T cells programmed to find GUCY2C-tagged cancer cells, the researchers found that they “provided long-term protection against lung metastases.”
The lung is a common site for secondary tumours in colorectal cancer in humans.
The mice that received CAR T-cell therapy lived for another 100 days with no secondary tumours, whereas the mice that received a control treatment only lived an average of 20 days after treatment.
Although this study did not test for any side effects that may have arisen from the engineered T cells going “off-target,” the researchers had previously shown, using a mouse version of the therapy, that there were “no off-target effects.”
Prof. Snook acknowledged the “major concern” about safety with using CAR T-cell therapy. “In other cancers,” he notes, “the field has observed lethal auto-immune responses.”
He said that there are ongoing efforts to create fast-acting antidotes to these off-target responses, but he and his colleagues believe that their study shows that GUCY2C CAR T-cell therapy “may be very effective and safe in cancer patients.”
They also saw wider applications of the therapy in other hard-to-treat cancers that also express the GUCY2C tumour antigen.
“The antigen we target for colorectal cancer,” explained Prof. Snook, “is one that is shared across several high-mortality cancers including esophageal and pancreatic cancer.”
“Taken together, 25 percent of people who die from cancer could potentially be treated with this therapy.”
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Illegal Abortions Responsible For Mysterious Deaths In Bauchi: State Govt
Bauchi State Government has revealed that the mysterious deaths recorded in the State has been as a result of illegal abortions.
An investigation carried out by the Bauchi State Primary Healthcare Development Agency has revealed that illegal abortion by unqualified medical practitioners is the cause of mysterious deaths in Azare and other local government areas in the northern part of the state.
According to reports, no fewer than 200 women have died in Bauchi as a result of this and there are projections that the number could be more at the end of the investigation.
The Executive Chairman of the agency, Dr Rilwanu Mohammed, disclosed this Friday, May 29, at an interactive session organized by the Bauchi State Public Health Media Network.
Mohammed said the deaths resulted from unwanted and unplanned pregnancies by both married and unmarried women of childbearing ages who, after becoming pregnant, visited quack health workers to terminate the pregnancies.
He said the lack of understanding of the importance of child spacing as well as ignorance of what to do with such pregnancies had become a major problem to family health in the state.
He emphasized the need for adequate sex education for the girl-child by parents, particularly mothers, to reduce unwanted pregnancies, thereby reducing deaths from complications.
Ondo Govt Arraigns Suspected Killers Of Funke Olakunrin
The Ondo State Government has arraigned four men suspected to have killed Mrs Funke Olakunrin, the daughter of the National Leader of Afenifere, Pa Reuben Fasoranti.
Recall that it was earlier reported that the Nigeria Police Force handed over the suspects to the State Government.
They are Lawal Mazaje from the Felele area of Kogi State, Adamu Adamu from Jada area of Adamawa State, Mohammed Usman from Illela area of Sokoto State, and Auwal Abubakar from Shinkafi area of Zamfara State.
The suspects were arraigned on Friday by the government at a Chief Magistrate Court sitting in Akure.
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The Corps Marshal, Lagos State Environmental Sanitation Corps (LAGESC), Gbemisola Akinpelu, gave the warning on Monday at the Command Headquarters in the Oshodi area of the state.
In a statement issued by the Head, Public Affairs Unit of LAGESC, Adebayo Kehinde noted that the order is coming from the State Ministry of Environment.
He reiterated the commitment of the agency to monitor markets across the state to ensure that the directive of the government is being adhered to strictly.
He urged the traders to maintain environmental cleanliness around the markets and stop trading on road setbacks and drainage.
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