CAR T-cell therapy is a type of immunotherapy that uses a person’s own immune cells to target multiple myeloma cells. It has shown strong results for some people with relapsed/refractory myeloma. Two CAR T-cell therapies targeting a protein called BCMA are already approved for use in later stages of the disease.

Researchers continue to study how to improve and expand access to these therapies. Clinical trials are now exploring new targets beyond BCMA, ways to deliver CAR T-cells directly into the body, and approaches that do not require using a patient’s own cells. Scientists are also testing CAR natural killer (NK) cell therapies, which may be safer and easier to produce.

This section reviews current clinical trials and new strategies being studied to make CAR T-cell and CAR NK cell therapies more effective and accessible in the treatment journey for people with multiple myeloma.

CAR T-cell therapies in clinical trials

There are 34 active clinical trials using CAR-T in the United States that include newer CAR-T technologies and additional CAR-T targets. If you want to explore which clinical trials are closer to you, or add more personalized filters you can create an account to access these features in HealthTree’s Clinical Trial Finder.

Reducing side effects 

The KITE anitocabtagene autoleucel (anito-cel) is still a BCMA therapy but doesn’t have any neurotoxicity because it uses the D-Domain instead. In the latest results from the iMMagine-1 trial, researchers highlighted durable responses in patients with relapsed or refractory myeloma.

Allogeneic off-the-shelf CAR T-cell therapy 

Traditional CAR T-cell therapy uses a patient’s own T cells, to be modified individually. This process can take weeks and may not be an option for those with rapidly progressing disease. In contrast, “off-the-shelf” CAR T cells are manufactured from healthy donors and stored for future use. These therapies are available immediately and may reduce delays, cost, and variation in quality between patients. 

• Off-the-shelf CAR T cells use healthy donor cells, which could make treatment more accessible.
• Strategies like EBV-specific T cells and gene editing may help reduce rejection and side effects.
• Early trials show favorable safety and response, especially in lymphoma.
• Research is ongoing to improve how long these cells stay active in the body.

New approaches 

Donor T cells can trigger immune reactions like graft-versus-host disease (GVHD) or be rejected by the patient's immune system. To avoid GVHD researchers have tried to remove native T cell receptors and engineer cells to evade rejection by natural killer (NK) cells. 

Some approaches use Epstein-Barr virus-specific T cells (EBV-VSTs), which naturally recognize viral proteins, and can be modified to carry CARs targeting cancer cells like CD19 or CD30.

Another main challenge of CAR therapy is availability. The current process involves a long manufacturing time, and the modified cells have a limited persistence in the body, meaning large costs and low long-term effects. Research is now focused on improving the therapy’s availability, including repeated dosing and changes to the manufacturing process. 

Explore clinical trials and use a personalized search to find the best option for you with HealthTree’s Clinical Trial Finder by creating a free account.

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Faster availability 

FasTCAR by Gracell is a new way of manufacturing CAR T-cells that can shorten the availability from weeks it took CAR-T to be ready, to next day manufacturing. It uses stabilized virus vectors to activate CAR-T.  

CAR NK cell therapy: A safer, off-the-shelf option in development

CAR NK (chimeric antigen receptor natural killer) cell therapy is an emerging treatment that uses natural killer (NK) cells, another type of immune cell, to recognize and respond to myeloma cells. 

Like CAR T-cells, NK cells can be genetically modified to target specific proteins on cancer cells, such as BCMA or CD70. However, NK cells do not need to match a patient’s immune system as closely, which reduces the risk of complications like graft-versus-host disease (GvHD).

Because NK cells can often be collected from healthy donors and stored, CAR NK therapies are being developed as off-the-shelf options that may be given more quickly than standard CAR T-cell therapies. 

Clinical trials are evaluating CAR NK cells targeting BCMA (NCT05652530) and CD70 (NCT05092451), especially in patients whose myeloma has returned after standard treatments. Researchers are also testing dual-target CAR NK therapies to help prevent relapse by addressing antigen loss.

Early results suggest that CAR NK therapy may offer a safer and more accessible option, though more studies are needed to confirm how long these cells last and how well they control the disease.

CAR-T by direct injection (in vivo CAR delivery)

To improve the availability of CAR-T, researchers are now studying a new approach called in vivo CAR T-cell therapy, where the genetic instructions to make CAR T-cells are delivered directly into the patient’s body, usually through a one-time infusion. This would work similarly to a vaccine. 

This method uses a viral or non-viral carrier to deliver the CAR gene straight to T cells inside the body, which may allow faster treatment without cell collection or manufacturing delays. 

One company, EpiVax Therapeutics (formerly EsoBiotec), has been developing this technique, and its early-stage technology was recently acquired by AstraZeneca to support further clinical research. While this strategy is still in early development, it has the potential to simplify how CAR T-cell therapy is delivered and increase access for more patients.

Keep reading about this method by clicking the button below.

A NEW WAY TO ENGINEER CAR-T