GO CAR T-CELLS! Chimeric Antigen Receptor (CAR) T-Cells: Fighting Cancer, Autoimmune Diseases, and Aging

“Engineered immune cells are being used to successfully treat people with a range of debilitating autoimmune conditions, such as, ulcerative colitis, rheumatoid arthritis, and lupus.”

Rachel Fieldhouse, Nature November 26, 2025

“CAR-T therapies are poised for significant growth as developers seek to extend the technology to solid tumors, autoimmune conditions, and other diseases.”

Science December 4, 2025

As a first year medical almost six decades ago, I remember sitting in my histology course and for the very first time learning about lymphocytes—a type of white blood cell in our immune system. (Histology is the study of healthy cells, tissue, and organs; the course prepares medical students for what comes up clinically in the pathology of disease.) I recall our professor telling the class that there were three kinds of lymphocytes: “large, medium and small.”  I thought, “Well…that’s not complicated.”

Fast forward 60 years. Scientists have now discovered so many sets and subsets of lymphocytes with so many different functions that it has become almost impossible to keep up. In this week’s Germ Gems post, I provide a review of Chimeric Antigen Receptor (CAR) T-Cells—a type of T lymphocyte. Given their promise in treatment of cancer, autoimmune diseases, and even aging, CAR T-cells are opening a new frontier in immunology.

The immune system (recap).The immune system is the body’s natural defense system. It is made up of a network of cells, molecules, tissues and organs working together to protect the body.

Lymphocytes occur in large numbers in the blood and lymph and in the lymphatic organs, such as the thymus, lymph nodes, and spleen. They are responsible for the specificity of adaptive immune responses.

In 1961, the French-Australian scientist Jacques Miller showed that the thymus gland produces lymphocytes essential for cellular immunity. His discovery led to the naming of "T cells" (thymus-derived) and differentiated these cells from B cells (bone marrow-derived). 

Together with macrophages, T cells provide “cell-mediated immunity” against a wide variety of intracellular microbes (bacteria, viruses, fungi, and parasites). In contrast, B cells and their products—immunoglobulins (antibodies)— provide “humoral immunity” against encapsulated bacteria plus many other kinds of microbes. “Innate immunity,” the first line of defense, is the purview of Natural Killer (NK) cells and neutrophils.

What are CAR-T cells? CAR T-cells are genetically engineered T lymphocytes designed to recognize and kill specific cells with high precision—most commonly, cancer cells.  CAR T-cell “chimeric antigen receptors” are synthetic and are made of three main parts: an extracellular binding domain to find cancer cells, a transmembrane domain to anchor it, and an intracellular signaling domain to activate the T cell to kill the tumor cell target.

CAR-T cells to treat cancer. CAR T-cells that are used to treat cancer are a patient's own T cells that have been genetically engineered in a lab to have Chimeric Antigen Receptors or CARs. The CARs recognize and attack specific proteins on cancer cells, turning the T cells into powerful, personalized cancer-killing cells that are then infused back into the patient.

The different steps in this process are complicated. They include: 

1. Collection: T cells are drawn from the patient's blood—a process called leukapheresis.

2. Genetic Engineering: In the lab, a gene for the CAR is added to the T cells, making them "CAR T-cells" that can target cancer.

3. Expansion: These modified CAR T-cells are grown in large numbers.

4. Chemotherapy (Preparation): The patient receives chemotherapy to clear space for the new CAR T- cells.

5. Infusion: The CAR T-cells are infused back into the patient, ready to hunt and kill cancer.

6. Monitoring: Patients are closely watched for side effects as the new cells begin their work.

   
   

(The Mayo Clinic’s online “CAR T-Cell Therapy Program—Overview” provides a detailed description of the process.) This cellular immunotherapy is highly effective for certain blood cancers (leukemia, lymphoma, and multiple myeloma) allowing the engineered T-cells to multiply, find, and destroy cancer cells, sometimes leading to long-lasting remission.

CAR-T cells to treat autoimmune diseases. CAR T-cell therapy is also an emerging and promising treatment for a number of autoimmune rheumatic diseases. These include systemic lupus erythematosus (lupus), rheumatoid arthritis, systemic sclerosis, autoimmune hemolytic anemia, and inflammatory bowel disease. According to rheumatologist Sneha Patel, MD, “[T]he appeal of this approach lies in its potential to eradicate pathogenic autoantibodies and induce durable clinical remission. Targeting and ‘resetting’ the B-cell compartment has long been a cornerstone of rheumatologic therapy, and CAR-T cell therapy represents a more profound and potentially transformative extension of this strategy.” (Patel, S., “CAR T-Cells Hold Major Promise for Patients With Lupus,” MedPage Today, January 5, 2026).

CAR-T cells to treat the consequences of aging (senescence). Pioneer researchers in CAR T-cell cancer therapy are now extending their work on cancer to combat diseases of aging. Instead of cancer cells, their new research focuses on engineering CAR T-cells to target and hunt down senescent cells which accumulate with age and drive inflammation and disease. Their research has shown promising results in mice for age-related diseases by using CAR T-cells to clear these harmful cells.

Building on the successes of their pioneering cancer therapies, this approach aims to treat chronic conditions like chronic obstructive pulmonary disease, metabolic syndrome, and neurodegenerative diseases by rejuvenating tissues. Recent findings have shown CAR T-cells can effectively clear senescent cells in mice, reducing inflammation and improving conditions like liver disease and, potentially, other age-related illnesses.

Role of the U.S. Food and Drug Administration in CAR T-Cell therapy. In 2017, the U.S. Food and Drug Administration (FDA) approved the world’s first CAR T-cell therapy. (Mahat, U., et al., “Advancing CAR T-Cell Therapy; Evidence-Based Trial Design for Chimeric Antigen Receptor T-Cell Therapy in Oncology,” JAMA, December 8, 2025). Since then, the agency has played a foundational, regulatory, and facilitative role in the development and adoption of CAR T-cell therapies. It has established guidelines to ensure their safety, quality, and efficacy, while actively working to broaden patient access. By June 2025, the FDA had approved seven distinct CAR T-cell therapies, moving from initially strict regulatory hurdles to a more streamlined framework that supports broader, faster adoption of these treatments.

The FDA has played a crucial role in developing and monitoring CAR T-cell therapies. The question is whether that will continue under the current administration’s leadership of the agency. (That is, Mr. Kennedy’s leadership as Secretary of the Department of Health and Human Services and the leadership of Vinay Prasad, a long-time critic of the agency, as director of the FDA’s Center for Biologics Evaluation and Research and as chief medical and scientific officer at the FDA.)

The recent departure of Dr. Richard Pazdur from the agency is of major concern. Pazdur is an expert in drug regulation and oncology; he worked for the FDA for 26 years and was the founding director of the agency’s oncology center. On November 11, 2025, Pazdur was appointed director of the FDA’s Center for Drug evaluation and Research (CDER), an appointment that was seen as a potentially stablizing force in the agency after a year of turmoil and tension. (He was the fourth leader of the CDER that year.) Less than a month later, however, Pazdur announced his retirement.

Commenting on his departure, Pazdur warned of “chaos at the agency.” (McCreary, J., “Pazdur Tells of FDA Turmoil,” MedPage Today, January 14, 2026). He said that he did not leave because he wanted to leave. Instead, he left because “promises were made but promises not kept.” He stated: “It’s terrible to see 25 years of work dismantled.”

The loss of Pazdur’s leadership at a time when CAR T-cell therapy is on the cusp of major breakthroughs in the treatment of so many human maladies (cancer, autoimmune diseases, and diseases of aging), is most unfortunate, to say the least. It raises concerns over the future direction of the CDER as well as the FDA’s ability to maintain its current pace of progress with CAR T-cell therapies. (Fidler, B., “Richard Pazdur, FDA drug czar, to retire from agency,” BioPharma Dive, December 2, 2025).