CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

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Schallen
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CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby Schallen » Tue May 01, 2018 12:12 pm

http://www.prweb.com/releases/2018/05/prweb15454899.htm

PHILADELPHIA (PRWEB) MAY 01, 2018
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 at the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health show that a type of immunotherapy called CAR-T cell therapy, successfully kills tumors and prevents metastases in mouse models of the disease. The work published in the journal Cancer Immunology Research, 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 and pancreatic cancer,” said Adam Snook, PhD, Assistant Professor in the department of Pharmacology & Experimental Therapeutics at Jefferson (Philadelphia University + Thomas Jefferson University). “Taken together, 25 percent of people who die from cancer could potentially be treated with this therapy.”
“Colorectal cancer rates are exceptionally high in our region, and advanced stage disease is difficult to treat. The concept of moving CAR-T cell therapy to colorectal cancer is a major breakthrough, and could address a major unmet clinical need. We are optimistic about the pre-clinical results,” said Karen Knudsen, PhD, Director of the Sidney Kimmel Cancer Center at Jefferson Health, one of only 69 NCI-Designated Centers in the US.
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. The antigen was identified as a potential biomarker and therapeutic target in colorectal cancer by Scott Waldman, MD, PhD, Chair of the Department of Pharmacology & Experimental Therapeutics at Jefferson, and a leader of the SKCC’s Gastrointestinal Cancer program.
Dr. Snook 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, Dr. Snook and colleagues 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. Although the current experiments were not designed to test for autoimmunity-related side effects, earlier work by Dr. Snook and colleagues demonstrated no off-target effects. In that study, the researchers used a mouse-version of the CAR-T therapy that had the potential to react to off-target mouse organs, but saw no adverse effects.
“Safety is a major concern for the CAR-T therapy approach. In other cancers, the field has observed lethal autoimmune responses,” said Dr. Snook. “Other researchers are developing fast-acting antidotes to CAR-T therapy to quell these safety concerns, but our data suggests that GUCY2C CAR-T therapy may be very effective and safe in cancer patients.”
The next steps for the researchers would be a phase 1 clinical trial in humans.

boswind
Posts: 74
Joined: Fri Apr 11, 2014 12:04 pm

Re: CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby boswind » Thu May 03, 2018 1:46 pm

Excellent info. Thank you.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4 inoperable
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.19 -01.20: Centuximab+Irinotecan
03.20 - 06.20: STIVARGA
07.20 - present: lonsurf+Avanstin
MSS, KRAS wt, BRAF wt
131 rounds of chemos received (as of 12.31.20)

boswind
Posts: 74
Joined: Fri Apr 11, 2014 12:04 pm

Re: CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby boswind » Thu May 03, 2018 1:58 pm

I am looking forward to good news of additional new potential treatments that will be presented in ASCO Anuual meeting jun 2018. For those of us who have late stage cancer if we can hang on 1-2 more years the survival duration will become much longer.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4 inoperable
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.19 -01.20: Centuximab+Irinotecan
03.20 - 06.20: STIVARGA
07.20 - present: lonsurf+Avanstin
MSS, KRAS wt, BRAF wt
131 rounds of chemos received (as of 12.31.20)

mhf1986
Posts: 158
Joined: Sat Mar 11, 2017 8:30 pm
Location: near DC

Re: CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby mhf1986 » Sun May 06, 2018 9:42 am

Is this the same type of study as the one we read about at Stanford a few months ago? I seem to remember they starting recruiting for the trial but only for Leukemia patients?
Caregiver to DH, dx @ 50, mets to liver/lungs, MSS, wild
9/16 CEA 114, blockage, left hemi, perm. colostomy
11/16 port in, FOLFOX + Avastin
6/17 CEA 15, 5FU + A only due to neuropathy
11/17 CEA 38, CAPOX + A
1/18 CAPOX = hi bilirubin/bad hfs, back to FOLFOX + A
5/18 growth; Vectibex + 75% Irinotecan
7/18 CEA 23, shrinkage
10/18 CEA 28, growth of 2 liver tumors/shrinkage of few and lung nodes
11/18 Lonsurf, looking at spheres, proton, trials
11/19/18 Peace

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henry123
Posts: 218
Joined: Sun Oct 08, 2017 3:25 am

Re: CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby henry123 » Sun May 06, 2018 10:56 am

A lot of optimism around Car T cell immunotherapy.
Hopefully it will be available soon as a standardised treatment for most types of cancers especially CRC.
46yo M msi-high Lynch +ve
5/16 lap AR 14/21 L nodes +ve
T4N2M1
7/16 Capox 9 cyc
9/16 cea 2
1/17 550
PET CT mets in lung & peri
iri+ avast fail
3/17 10577
4/17 regro fail
5/17 cea 28800
5/17 CT inc in size of mes nodes ,onset of multi nodules in liver
6/17 Opdivo start
7/17 26754
8/17 5623
9/17 497
10/17 52
CT all clear exc a nodule in Lung. liver norm
1/18 3.6
Aspirin start
6/18 1.5 CT clear
12/18 1.1 NED
1/20 NED Opdivo stop
8/23 1.0 All ok

some808guy
Posts: 10
Joined: Thu Oct 01, 2015 2:38 am

Re: CAR-T Immunotherapy Eliminates Metastatic Colorectal Cancer in Mice

Postby some808guy » Mon May 07, 2018 8:09 pm

mhf1986 wrote:Is this the same type of study as the one we read about at Stanford a few months ago? I seem to remember they starting recruiting for the trial but only for Leukemia patients?



I believe this is different. The one at Stanford utilizes 2 immunotherapy drugs in combination.
This one basically grows your T-Cells then reinjects them into you.

Has been done for multiple other cancers but I guess this is news because it targets a specific antigen found in CRC.


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