CAR-T Therapy Eliminates Metastatic Colorectal Cancer in Mice

Chimeric antigen receptor T-cell (CAR-T) therapies are a very promising form of cancer immunotherapy. Initially developed for use against blood cancers, they are now showing their worth in the treatment of solid tumors. The most important aspect of this technology platform is not that it is effective, but rather that it can be adapted at an incremental cost to many types of cancer. The future of cancer treatment is entirely determined by choice of strategy: without a broadly applicable therapy with a low cost of adaptation, or ideally a universal therapy that can be applied as-is to any cancer, then there are too few researchers and far, far too many different types of cancer for the progress we'd like to see. If we wish to see cancer controlled in our lifetimes, then the development of general therapies that can be applied to most or all types of cancer is a requirement.

Immunotherapy has given patients and oncologists new options, which for some patients, has meant cures for diseases that had been untreatable. Colorectal cancer has a high mortality rate in advanced stages of the disease with few effective therapies. Researchers have shown that a type of immunotherapy called CAR-T cell therapy, successfully kills tumors and prevents metastases in mouse models of the disease. The work is the last step of preclinical testing prior to human clinical trials. "The antigen we target for colorectal cancer is one that is shared across several high mortality cancers including esophageal cancer and pancreatic cancer. Taken together, 25 percent of people who die from cancer could potentially be treated with this therapy."

CAR-T immunotherapy involves removing a patient's immune cells, engineering them to target the tumor (and only the tumor) and then multiplying those cells en masse before infusing them back into the patient. This powerful burst of targeted immune cells, quickly overcomes the cancer's own immune-suppression to kill the tumors, but requires a marker or homing beacon specific to the cancer. For colorectal cancer that beacon, or tumor antigen, is called GUCY2C. Researchers created a CAR-T therapy made specifically to treat GUCY2C-expressing cancers such as colorectal cancer.

In this study, the researchers tested a human-ready version of the therapy in mice. They showed that mice with human colorectal tumors treated with CAR-T therapy successfully fought the tumor cells. All of the mice studied survived without side effects for the duration of the observation period - or 75 days, compared to a 30-day average survival of mice with control treatment. In order to more closely replicate late-stage disease in humans, researchers also looked at a mouse model of colorectal cancer that developed lung metastases, a common site for metastasis in colorectal cancer patients. Mice that were treated with the CAR-T therapy survived over 100 days with no metastases, whereas the control group survived an average of 20 days. The next steps for the researchers would be a phase 1 clinical trial in humans.

Link: https://www.eurekalert.org/pub_releases/2018-05/tju-cie050118.php

Comments

I hope they are keeping data on the treated mice after their cancer is in remission to see if there are any otherwise beneficial side effects. Wouldn't it be great if there was a standard blood test for cancer that could be analyzed overnight and have a routine of shots ready the next day?

Is there a particular immune cell, or could we make one, that goes after senescent cells?

Posted by: Tom Schaefer at May 8th, 2018 7:36 AM

It is a very promising approach. But I am skeptical about the mice models of cancer. Human tumors take many years to develop and after chemo one can leave many years in remission . The mice have such a short life span that their cancers have to be boosted artificially. At leats the immunotherapy looks to be fighting the tumors and not the artificial model. Before going to humans I would try of did or cats. They love longer and have similar lifestyle issues as humans.

Posted by: Cuberat at May 8th, 2018 7:49 AM

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