MMRF invests $1M to advance DCT’s new CAR T-cell therapy

Developer on track for clinical testing in myeloma patients over next 2 years

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A pig-shaped bank is seen making a 'yum' face as coins and bills fly into its top slot.

Through its Myeloma Investment Fund, the Multiple Myeloma Research Foundation (MMRF) has invested $1 million in novel CAR T-cell technology from Dynamic Cell Therapies (DCT) that aims to better treat multiple myeloma.

Backed by this investment, DCT remains on track to move a new CAR T-cell therapy into clinical testing in people with relapsed and refractory multiple myeloma over the next two years.

“The support of the MMRF & the Myeloma Investment Fund provides key expertise that will enable us to hasten the development of novel and best-in-class CAR-T cell therapies for patients with relapsed and refractory multiple myeloma,” Fred Mermelstein, PhD, DCT’s CEO, said in a company press release.

According to the release, “DCT is developing technology platforms that will allow CAR-T cells to attack unique … tumor targets that will allow for durable responses to treatment.”

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Many myeloma patients seen to relapse despite treatment

Multiple myeloma is a blood cancer in which abnormal plasma cells — a type of immune cells that produce antibodies — grow out of control in the bone marrow and crowd out normal immune cells that help fight infection, causing the disease’s symptoms.

Despite the therapeutic options available, multiple myeloma can be difficult to treat because it often is refractory, meaning it does not respond well to therapy or becomes resistant to it. Additionally, the cancer often is relapsing, meaning it returns after treatment.

CAR T-cells have emerged as a therapeutic option for many types of blood cancer, including multiple myeloma. This type of therapy involves modifying a patient’s immune T-cells with a chimeric antigen receptor, or CAR, that can recognize specific cancer proteins.

These modified T-cells are then infused back into the patient’s blood, where they travel toward cancer cells and destroy them.

But despite the benefits seen with the recently approved CAR T-cell therapies Carvykti (ciltacabtagene autoleucel) and Abecma (idecabtagene vicleucel), “many patients with multiple myeloma still relapse after therapy,” Mermelstein said.

In addition, overactive CAR T-cells often lead to side effects and dose-limiting toxicities.

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MMRF calls DCT’s cell therapy strategy ‘cutting edge’

To overcome these issues, DCT developed a CAR T-cell technology in which cancer cell targeting is uncoupled from CAR T-cell activation. These CAR T-cells recognize a chemically inactive small molecule that is conjugated, or bound, to an antibody that targets a specific cancer molecule.

When they bind to the small molecule-antibody conjugate bound to cancer cells, CAR T-cells release proteins that form holes in the cancer cell’s membrane, leading to their death. At the same time, activated CAR T-cells release immune signaling molecules that recruit other immune cells to fight the cancer.

By controlling the amount of the small molecule-antibody conjugate that is given to a patient along with CAR T-cells, physicians are expected to be better able to control the cells’ activity, reducing the risk of side effects.

For example, administering higher doses of the antibody conjugate will boost the immune attack against cancer, while lower doses will minimize harm to normal cells.

Further, the same small molecule can be conjugated to different antibodies targeting other cancer molecules, which could improve CAR T-cells’ ability to kill cancer cells, even when mutations arise as a mechanism to escape the effects of CAR T-cell therapies.

At the MMRF, we are deeply committed to advancing novel treatments intended to improve patient outcomes and get us closer to cures. … We are energized by DCT’s cutting-edge cell therapy approach as a potentially transformative answer to patients with relapsed or refractory myeloma.

Preclinical work led by researchers from DCT showed that small molecule-activated CAR T-cells expanded more rapidly in number, produced more immune molecules, and were better at killing cancer cells. In a mouse model of multiple myeloma, these CAR T-cells showed better long-term cancer control than did Carvykti and Abecma alone.

“At the MMRF, we are deeply committed to advancing novel treatments intended to improve patient outcomes and get us closer to cures,” said Michael Andreini, MMRF’s president and CEO.

“We are energized by DCT’s cutting-edge cell therapy approach as a potentially transformative answer to patients with relapsed or refractory myeloma,” Andreini added.

The Myeloma Investment Fund is a philanthropy fund that provides financial and strategic support to advance new potential therapies for multiple myeloma. All of its profits are reinvested into ongoing research until a cure is found.