Researchers continue to study how to improve and expand access to these therapies. Clinical trials are now exploring new targets, faster 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 lymphoma.

What research is focusing on now

Scientists are working to make CAR-T more consistent and easier to receive. CAR-T uses a person’s own T cells, a type of white blood cell, that are engineered to recognize a target on lymphoma cells.

• Broader targets. New CAR-T options aim at more than one target at once. A dual-target CAR uses two binding parts so it can recognize lymphoma cells that change their surface markers. An ongoing study for bispecific CAR-T for non-Hodgkin lymphoma, large B-cell lymphoma, diffuse large B-cell (NCT05421663) is assessing a new CAR T-cell therapy for people who have never received it.  
• Off-the-shelf options. Allogeneic means cells come from a healthy donor instead of the patient. Developing CAR-T treatments that use donor cells instead of the patient’s cells could shorten wait times and make treatment available when a person’s own T cells are low.
• Built-in safety features. Safety switches are genetic on-off controls that allow the team to stop or dial down CAR-T activity if needed. Click here to learn more.
• More durable responses. Armored CARs are designed to release helpful immune signals, allowing T-cells to continue functioning in the lymphoma environment. Click here to learn more.
• Earlier use in care. Trials are testing CAR-T sooner in care for some B-cell lymphomas, sometimes after one line of therapy instead of many.
• Care setting. Some studies are evaluating outpatient care models with closer home monitoring to reduce hospital time. 

Expanding beyond current lymphoma subtypes

Numerous clinical trials on therapies targeting blood cancers are currently ongoing globally, with the United States and China at the forefront of CAR T-cell research. Many studies focus on expanding options for lymphoma types that currently lack approved CAR-T treatments.

• T-cell lymphomas. This type of lymphoma is challenging because the targets on T-cell lymphoma can also be on healthy T-cells. Strategies under study include target-sparing designs and temporary switches to protect healthy cells. 
• Hodgkin lymphoma. Trials are exploring CAR-T against CD30, a surface protein found on most classical Hodgkin lymphoma cells.
• Low-grade and rare B-cell lymphomas. Studies are testing new targets and dual-target CARs for marginal zone lymphoma, small lymphocytic lymphoma, and Waldenström macroglobulinemia. 
• Natural killer cell therapies. Natural killer cells are part of the immune system that can be engineered with CARs. These may be used alone or combined with T-cell approaches.

Questions to ask the clinical trial team 

• What target does the CAR recognize and why is it relevant for my subtype?
• What are the steps, timelines, and monitoring plan?
• If I respond, what follow-up is planned and for how long?
• If I do not respond, what options remain?

Clinical trials are voluntary. Your care team can help you weigh expected benefits, risks, and the time needed. Keeping a simple list of your past treatments and dates can speed up trial matching.

EXPLORE CAR-T CLINICAL TRIALS FOR LYMPHOMA

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 utilizes a viral or non-viral carrier to deliver the CAR gene directly to T-cells within the body, potentially enabling faster treatment without delays associated with cell collection or manufacturing. 

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 its early development, it has the potential to simplify the delivery of CAR T-cell therapy and increase access for more patients.

Keep reading about this method by clicking the button below.

A NEW WAY TO ENGINEER 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 lymphoma cells. 

Like CAR T-cells, NK cells can be genetically modified to target specific proteins on cancer cells, for example, CD-19 in B-cell lymphoma cells. 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.