Cell Therapy: Expanding Beyond Cancer
Author: Garry Coulson, Ph.D.
Historically focused on cancer treatments, cell therapies have steadily been advancing into non-oncology indications. The success of chimeric antigen receptor T (CAR T) cells in treating hematologic malignancies has demonstrated that immune cell reprogramming can deliver long-lasting, potentially curative outcomes. Building on the success of CAR T cells, cell therapies are now being applied to other chronic conditions. In part, this is driven by an improved understanding of disease biology and identification of new targets in a wide array of chronic disease, including autoimmune, cardiovascular, and fibrotic disorders.
What are CAR T Cells?
CAR T cells are personalized cell therapies traditionally created by modifying a patient’s own (autologous) T cells ex vivo to express a synthetic receptor, called a CAR, which recognizes and binds to specific disease markers (antigens) present on the surface of target cells. Once bound, the CAR T cells are activated to destroy the harmful cells. This effectively transforms the patient’s immune system into a powerful and precise therapeutic tool. More recently, the use of allogeneic (donor) CAR T cells is currently being explored to overcome some of the limitations of autologous approaches, such as long manufacturing time and variability in quality. The transformation of T cells in vivo is also a novel approach being evaluated. This is intended to simplify manufacturing and enable direct reprogramming inside the patient’s body, reducing cost and treatment delays.
At the time of writing, seven CAR T cell therapies have been approved by the US Food and Drug Administration (FDA) for various blood cancers (Table 1).
| Therapy (Generic Name) | Indication(s) | FDA Approval Date(s) | Company |
|---|---|---|---|
| Kymriah (tisagenlecleucel) | Pediatric/young adult relapsed/refractory B-cell precursor ALL; adult relapsed/refractory large B-cell lymphoma | Aug 2017; May 2018 | Novartis |
| Yescarta (axicabtagene ciloleucel) | Adult relapsed/refractory large B-cell lymphoma; follicular lymphoma | Oct 2017; Mar 2021 | Kite Pharma (Gilead) |
| Tecartus (brexucabtagene autoleucel) | Adult relapsed/refractory mantle cell lymphoma; B-cell precursor ALL | Jul 2020; Oct 2021 | Kite Pharma (Gilead) |
| Breyanzi (lisocabtagene maraleucel) | Relapsed/refractory large B-cell lymphoma; marginal zone lymphoma | Feb 2021; Dec 2025 | Bristol-Myers Squibb |
| Abecma (idecabtagene vicleucel) | Relapsed/refractory multiple myeloma | Mar 2021 | Bristol-Myers Squibb / bluebird bio |
| Carvykti (ciltacabtagene autoleucel) | Relapsed/refractory multiple myeloma | Feb 2022 | Janssen / Legend Biotech |
| Aucatzyl (obecabtagene autoleucel) | Relapsed/refractory B-cell precursor ALL | Nov 2024 | Gilead / Arcellx |
Table 1: FDA Approved CAR T Cell Therapies
Emerging Non-Oncology Applications
As noted previously, research (both preclinical and clinical) is currently underway to investigate the potential of CAR T cells for the treatment of various non-oncology chronic conditions. Some representative examples of such applications are summarized below.
Autoimmune Diseases
In several autoimmune disorders (e.g., lupus, rheumatoid arthritis, and ulcerative colitis), autoreactive B cells contribute to disease pathology by producing harmful antibodies that attack healthy tissues and drive the chronic inflammatory response. Treatment with CAR T cells aims to “reset” the immune system by eliminating these destructive B cells, thereby reducing inflammation and halting disease progression. Unlike traditional treatments that rely on the chronic use of immunosuppressants, CAR T therapy has the potential to offer long-term remission after a single intervention.
Neurological Disorders
Exploratory research suggests CAR T cells may also help in certain neurological conditions and neurodegenerative diseases (e.g., myasthenia gravis and multiple sclerosis). Since these neurological conditions may be associated with an autoimmune etiology, CAR T cells can be used to remove harmful antibody-producing immune cells or clear protein aggregates linked to neurodegeneration. This precision targeting approach could complement existing therapies and address underlying disease mechanisms rather than relying on the management of symptoms alone.
Chronic Infections
CAR T cell therapy is also being studied as a relatively novel way to tackle chronic infections (e.g., human immunodeficiency virus [HIV]) which can persist in certain cell reservoirs despite long-term treatment. In an attempt to combat this, researchers are now exploring the use of CAR T cells to find and destroy infected cells by targeting unique viral proteins that may be expressed on the cell surface. This approach could help to clear out hidden virus reservoirs and keep the virus under control or, better yet, could even lead to a functional cure. Unlike current treatments that typically only suppress the virus, CAR T cells aim to eliminate the infected cells entirely, thereby reducing the need for ongoing antiviral medication and potentially opening up avenues for one-time treatment.
Fibrotic Disorders
Fibrotic diseases, like those affecting the heart, liver, and lungs, typically happen when scar tissue builds up in the affected organs and damages the normal organ function. To target these fibrotic diseases, CAR T cells are being investigated as a method to specifically target cells which are key drivers of the scarring process (e.g., fibroblasts expressing fibroblast activation protein [FAP]). By removing these harmful fibroblasts, CAR T therapy could slow down or even reverse fibrosis, helping tissues heal and function properly again.
Beyond CAR T: Other Cell-Based Strategies
In the decade since their first approval, CAR T cells have had a remarkable impact on how we care for patients with blood cancers. Given their success, the use of CAR T cells is unsurprisingly expanding into other therapeutic areas, such as non-oncology immune-mediated diseases (noted above). However, CAR T cells are relatively less suited as a treatment modality for many genetic disorders. Since most genetic conditions result from the expression of non-functional or faulty structural or metabolic proteins and are not a product of rogue immune cells, depleting immune cells would typically not represent an effective treatment approach for these diseases. Therefore, other non-CAR T cell-based approaches are needed for these diseases and disorders.
Hematopoietic stem cell transplantation (HSCT)
HSCT, also referred to as a bone marrow transplant, remains a key treatment option for certain immunodeficiencies, blood disorders, and lysosomal storage disorders. In principle, HSCT is a therapeutic approach used to treat severe immune-related disorders by “resetting” a patients dysfunctional immune system through the act of replacing their faulty stem cells with healthy cells obtained either from the patient (autologous) or a healthy donor (allogeneic) thereby restoring normal immune function. These stem cells, typically derived from bone marrow, peripheral blood, or umbilical cord blood, have the capacity to regenerate all blood cell lineages, including immune cells.
Induced pluripotent stem cell (iPSC)
iPSC therapies typically utilize patient-derived cells that have undergone a process of “reprogramming” back into a pluripotent state, meaning they have the potential to develop into any cell type in the body. These autologous iPSCs can subsequently be genetically modified to correct any mutations (genetic errors) or express functional proteins (e.g., therapeutic enzymes, or regenerative trophic factors) necessary to achieve their therapeutic effect through their anticipated mode of action. After modification (if applicable), the iPSCs are then differentiated into the desired cell type, and reinfused back into the patient. This approach opens doors for regenerative treatments for various diseases, including heart and neurological diseases.
Together, these two approaches complement the CAR T cell methods by attempting to address the root cause of disease.
Clinical Trials
Representative examples of clinical trials evaluating the use of cellular therapies for non-oncology applications are shown below (all data provided are from public sources).
Sponsor: Cabaletta Bio, Inc. (https://www.cabalettabio.com/)
- Trial Name: RESET-SLE
- gov ID: NCT06121297 (https://clinicaltrials.gov/study/NCT06121297)
- Phase: 1/2
- Disease Indication: Systemic lupus erythematosus (SLE) and lupus nephritis (LN)
- Investigational Product: CABA-201
Sponsor: Kyverna Therapeutics (https://kyvernatx.com/)
- Trial Name: KYSA-6 / KYV101-006
- gov ID: NCT06192889 (https://www.clinicaltrials.gov/study/NCT06193889)
- Phase: 2/3
- Disease Indication: Myasthenia gravis
- Investigational Product: KYV-101
Sponsor: Beam Therapeutics (https://beamtx.com/)
- Trial Name: BTX-AUT-001 (BEACON)
- gov ID: NCT05456880 (https://clinicaltrials.gov/study/NCT05456880)
- Phase: 1/2
- Disease Indication: Sickle Cell Disease
- Investigational Product: BEAM-101
Sponsor: UCSF (https://www.ucsf.edu/)
- Trial Name: 20-31976
- gov ID: NCT04648046 (https://clinicaltrials.gov/study/NCT04648046)
- Phase: 1/2
- Disease Indication: Human immunodeficiency virus (HIV)
- Investigational Product: LVgp120duoCAR-T
The Outlook
With continuous advances in the development of gene delivery systems, precise genome engineering methods, and universal donor platforms, cell therapies are uniquely positioned to transform patient care for an expanding array of chronic non-oncology conditions. The ultimate goal with this approach is to hopefully move beyond symptom management and chronic medication requirements to delivering permanent cures through one-time treatments.
Regulatory Oversight and Ethical Review
Cell therapy trials for oncology and non-oncology diseases operate under rigorous regulatory frameworks to ensure patient safety and scientific integrity. Institutional Review Boards (IRBs) play a critical role in evaluating study protocols for ethical compliance, informed consent, and risk-benefit balance. In parallel, Institutional Biosafety Committees (IBCs) assess the safe handling of genetically modified cells and gene editing machinery and ensure adherence to biosafety standards.
Sabai's Role
At Sabai, we work with Sponsors and CROs advancing cell and gene therapies, to guide them through the complex regulatory landscape making sure every study meets the highest ethical and biosafety standards.
Connect with our IRB & IBC experts to ensure your study stays firmly grounded in compliance and compassion.