ICT’s CAR T-cell Therapy Shows Promise in Reducing Size of Solid Tumors

ICT’s CAR T-cell Therapy Shows Promise in Reducing Size of Solid Tumors
5
(4)

A potential CAR T-cell therapy by Innovative Cellular Therapeutics (ICT) showed early signs of safety and efficacy, significantly reducing tumor size in four patients with thyroid or colorectal cancer, new data show.

These findings will be shared in two presentations this Friday, May 15, at the ongoing 23rd American Society of Gene & Cell Therapy Annual Meeting, held online this year because of COVID-19. The presentations are titled “CoupledCARTM Technology for Treating Thyroid Cancer” (page 554) and “Novel CoupledCARTMTechnology for Treating Colorectal Cancer” (page 555).

CAR T-cell therapy is a type of immunotherapy that involves collecting a patient’s own immune T-cells and modifying them to produce a chimeric antigen receptor, or CAR. These cells are then returned to the patient to better recognize and eliminate cancer cells.

Despite its success in treating blood cancers — e.g., leukemia, lymphoma, and myeloma — CAR T-cell therapies have had little success in solid tumors.

In addition to a lack of cancer-specific targets, CAR T-cells have limited ability to penetrate and remain alive in solid tumors.

ICT generated CAR-T cells using a novel technology, called CoupledCAR, to overcome some of the limitations of current CAR T-cell therapies.

“CoupledCAR is ICT’s novel, in-house developed, proprietary CAR-T platform technology designed to overcome the challenges observed with conventional CAR-T therapies in treating solid tumors,” Larry (Lei) Xiao, PhD, founder and CEO of ICT,  said in a press release.

Preclinical studies have shown that CoupledCAR significantly improved the cells’ proliferation and enhanced their ability to infiltrate tumors, inducing more potent anti-tumor responses.

“CoupledCAR significantly improves the expansion of CAR-T cells in vivo and enhances the CAR-T cells’ migration ability and resistance to immunosuppression in the tumor microenvironment,” Xiao added. “This allows the CoupledCAR CAR-T cells to infiltrate tumor tissue sites and increase anti-tumor activities.”

Subsequently, ICT has conducted two studies in China to assess the safety and efficacy of CoupledCAR T-cells in patients with thyroid cancer and those with colorectal cancer.

The CAR T-cells for thyroid cancer were engineered to target the thyroid stimulating hormone receptor (TSHR), a protein with high levels in thyroid cancer cells. Experiments in animals showed that these CAR T-cells suppressed the proliferation of TSHR-positive tumor cells.

Two patients with advanced, hard-to-treat thyroid cancer — whose disease returned following thyroid surgery or did not respond to treatment — received CAR T-cells targeting TSHR.

The first patient was a 64-year-old man with papillary thyroid carcinoma, and the second was a 60-year-old woman.

After the patients were infused with CoupledCAR T-cells, the researchers saw a rapid proliferation of the cells with anti-tumor activity, with both patients showing a partial response (cancer size reduction) to the therapy.

One month after infusion, the lymph node metastasis in the first patient became undetectable. The size of his thoracic paratracheal nodules also decreased significantly.

Three months following infusion, the tumor size was markedly smaller compared to the one-month analysis.

After one month, the second patient experienced a volume reduction of 67.5% in a tumor located in the right lower lobe of the lung. Two months later, the reduction reached 73.5%. A parameter of malignancy, called standardized uptake value, decreased from 14.9 to 2.8 — a near complete response.

“We show that TSHR is a good target for treating thyroid cancer, and our anti-TSHR CoupledCAR T cells are safe and effective for treating thyroid cancer,” the researchers wrote.

In a second presentation, investigators discuss the results of CoupledCAR T-cells engineered to target a protein called guanylate cyclase 2C in two patients.

The first patient was a 55-year-old man, previously treated with eight cycles of XELOX chemotherapy, and one dose of radiotherapy. He underwent surgery followed by additional chemotherapy, but the cancer returned with metastases in the prostate and left lung.

The second patient was a 57-year-old woman, who received treatment with the chemotherapy agent Xeloda (capecitabine), followed by surgical removal of her rectal cancer. Despite additional chemotherapy, the patient developed metastasis.

One month following ICT’s CAR T-cell treatment, the tumor of the first patient was reduced by approximately 45%, and most of his target lesions by more than 50%.

In turn, the left lung tumor in the second patient was reduced by approximately 75%.

“The clinical data demonstrated that CoupledCAR-T cells effectively expanded, infiltrated tumor tissue sites, and kill tumor cells in patients with colorectal cancer,” the researchers wrote.

Patient enrollment is still ongoing to further test the safety and efficacy of CoupledCAR T-cells for thyroid and colorectal cancer, ICT said.

The company is also expanding its technology to treat additional solid tumors.

“We are excited to share the strong human proof-of-concept efficacy results achieved with CoupledCAR in China and have initiated … discussions with the [U.S. Food and Drug Administration] to advance our CoupledCAR solid tumor CAR-T therapies into the clinic in the United States in the near future,” said Xiao.

Total Posts: 48
José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

How useful was this post?

Click on a star to rate it!

Average rating 5 / 5. Vote count: 4

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?