How many FDA approved Immune cell therapy are there?

Introduction to Immune Cell Therapy

Definition and Types
Immune cell therapies (also known as cellular immunotherapies) constitute the treatment modalities in which immune cells are harvested from a patient (or a donor), manipulated ex vivo (e.g., expanded, activated, or genetically modified), and then reinfused into the patient to target cancer cells or other disease-related targets. These therapies encompass several distinct types of products. For example, treatments based on chimeric antigen receptor (CAR) T cells have garnered significant attention and include products such as tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel. In addition, dendritic cell–based products such as Sipuleucel-T (Provenge®) and tumor-infiltrating lymphocyte (TIL) therapies – now evolving into treatments such as Iovance’s Amtagvi (lifileucel) – are also considered immune cell therapies. The diversity of these products reflects different strategies of harnessing the immune system: some therapies boost the activity of a patient’s existing adaptive immunity, while others involve tailoring and engineering cells with specific receptors to overcome tumor immunosuppression.

Importance in Modern Medicine
The importance of immune cell therapies in modern medicine cannot be overstated. These therapies have transformed treatment paradigms especially in oncology because conventional treatments such as chemotherapy and radiation therapy have often been associated with high toxicity and limited durable responses. In some hematologic malignancies and even in certain solid tumors, immune cell therapies have demonstrated the potential to achieve long-term remission due to their ability to persist, expand, and mediate cytotoxic effects against cancer cells. That immune cells can “remember” and adapt to continuing antigenic challenges explains the durable responses observed in patients treated with these innovative therapies. Consequently, immune cell therapies now represent a critical component of the modern “living drug” approach and also offer hope in conditions where the immune system previously could not be harnessed effectively.

FDA Approval Process for Immune Cell Therapies

Overview of the FDA Approval Process
The U.S. Food and Drug Administration (FDA) plays a pivotal role in ensuring that new immunotherapeutic products meet rigorous safety, efficacy, and manufacturing standards before they can be marketed. The process entails a comprehensive review of preclinical data, clinical trial results, and manufacturing quality controls. For immune cell therapies, the FDA’s Center for Biologics Evaluation and Research (CBER) is principally responsible for evaluating these products. The review process begins with an Investigational New Drug (IND) application where sponsors present detailed preclinical studies demonstrating proof-of-concept and safety in animal models. Following IND clearance, clinical trials are conducted in phases (Phase 1 for safety and dose-finding, Phase 2 for preliminary efficacy and further safety data, and Phase 3 for large-scale efficacy) before a Biologics License Application (BLA) is submitted for final marketing authorization.

Specific Criteria for Immune Cell Therapies
Immune cell therapies face unique challenges compared to traditional small-molecule drugs. Because these products consist of living cells, the FDA places special emphasis on aspects such as product characterization, manufacturing consistency, potency assays, and biodistribution evaluations. For example, assays to determine the potency of genetically modified cell products or to verify the expression of chimeric antigen receptors are critical. Furthermore, the potential for long-term persistence and the associated safety issues (like cytokine release syndrome or neurotoxicity) require that clinical trial endpoints be carefully designed and monitored. In addition, the FDA requires rigorous evaluation of the genetic modifications (if used), sterility, and potential off-target effects in these products. Overall, these specific criteria have led to a highly structured and iterative regulatory pathway, ensuring that only those products meeting stringent safety and efficacy standards are approved.

Current FDA Approved Immune Cell Therapies

List and Description of Approved Therapies
Based on a comprehensive review of the Synapse sources and current literature, as of now, the FDA has approved the following immune cell therapies:

1. Sipuleucel‑T (Provenge®)
Sipuleucel‑T was the first autologous cellular immunotherapy approved by the FDA (in 2010) for metastatic castration‑resistant prostate cancer. It is prepared by isolating peripheral blood mononuclear cells (PBMCs) from the patient, exposing these cells to a fusion protein composed of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony‑stimulating factor (GM‑CSF), and then reinfusing the activated cells into the patient. This therapy marked a turning point in cancer immunotherapy by demonstrating that manipulating the patient’s own immune system could lead to clinical benefit.

2. Tisagenlecleucel (Kymriah®)
Tisagenlecleucel is a CAR T‑cell therapy that was approved in 2017 for the treatment of pediatric and young adult patients with B‑cell acute lymphoblastic leukemia (B‑ALL) and later for certain types of diffuse large B‑cell lymphoma (DLBCL). This therapy involves collecting T cells from the patient, engineering them to express a CAR that targets CD19, and then expanding and reinfusing the modified cells. It was one of the first CAR T‑cell products to demonstrate durable responses in hematologic malignancies.

3. Axicabtagene Ciloleucel (Yescarta®)
Approved also in 2017, axicabtagene ciloleucel is another CD19‑targeted CAR T‑cell therapy indicated for the treatment of relapsed or refractory large B‑cell lymphoma, including certain cases of primary mediastinal B‑cell lymphoma. This product uses a different viral vector and manufacturing process compared to tisagenlecleucel, and it is known for its rapid expansion and potent antitumor responses.

4. Brexucabtagene Autoleucel (Tecartus®)
Brexucabtagene autoleucel is a CAR T‑cell therapy approved for relapsed or refractory mantle cell lymphoma. It represents a further evolution in CAR T‑cell technology by addressing the unique biology of mantle cell lymphoma and has demonstrated high objective response rates in clinical trials. Its approval underscores the expansion of immune cell therapies into diverse lymphoid malignancies.

5. Idecabtagene Vicleucel (Abecma®)
Idecabtagene vicleucel is a CAR T‑cell therapy approved for multiple myeloma. It targets the B‑cell maturation antigen (BCMA) on myeloma cells and represents a significant breakthrough given the limited treatment options available for patients with relapsed or refractory multiple myeloma. The product’s approval was based on clinical data demonstrating durable and deep responses.

6. Ciltacabtagene Autoleucel (Carvykti®)
Also approved for the treatment of multiple myeloma, ciltacabtagene autoleucel is another BCMA‑targeted CAR T‑cell therapy. It has been shown to produce high overall response rates and is distinguished by its unique CAR design and binding affinity. This approval further solidifies the role of CAR‑T cell therapies in managing refractory hematologic cancers.

7. Lifileucel (Amtagvi®)
Recently, Iovance Biotherapeutics’ lifileucel, marketed as Amtagvi, received FDA approval for the treatment of advanced melanoma. As a tumor‑infiltrating lymphocyte (TIL) therapy, it is derived from a patient’s own tumor tissue. The cells are expanded ex vivo and reinfused into the patient, where they exert antitumor effects. This therapy is significant because it extends the reach of immune cell therapies into solid tumors where the immune environment is highly complex.

Together, these seven products represent the core of currently FDA-approved immune cell therapies. They reflect a range of technologies—from antigen‑presenting cell vaccines (Sipuleucel‑T) to various generations of CAR T‑cell therapies targeting different antigens—as well as TIL-based approaches for difficult-to-treat solid tumors. This diversity in mechanisms highlights the innovation in the field and confirms that, at this time, there are a total of seven FDA-approved immune cell therapies.

Indications and Usage
Each approved product has a distinct indication, reflecting the disease context and the underlying biological rationale:

- Sipuleucel‑T (Provenge®) is used for metastatic castration‑resistant prostate cancer in patients with minimal or no symptoms, offering an immunomodulatory effect that prolongs overall survival without necessarily shrinking tumors dramatically.
- Tisagenlecleucel (Kymriah®) is indicated for pediatric and young adult patients with relapsed or refractory B‑ALL and for adult patients with certain types of DLBCL. Its indication highlights the importance of targeting CD19 in B‑cell malignancies.
- Axicabtagene Ciloleucel (Yescarta®) is approved for patients with relapsed or refractory large B‑cell lymphoma and offers a potent therapeutic option for patients who have exhausted conventional treatment options.
- Brexucabtagene Autoleucel (Tecartus®) specifically targets mantle cell lymphoma, which is known for its aggressive biology and limited treatment options, thereby broadening the impact of CAR T‑cell therapies beyond the more common B‑cell lymphomas.
- Idecabtagene Vicleucel (Abecma®) and Ciltacabtagene Autoleucel (Carvykti®) target BCMA on myeloma cells to help treat relapsed or refractory multiple myeloma. Both have been shown to produce high response rates with manageable toxicity profiles, representing major strides in the management of this historically difficult disease.
- Lifileucel (Amtagvi®) is used in advanced melanoma patients, particularly those who have progressed following checkpoint inhibitor therapy. This therapy utilizes the naturally occurring TILs to mediate antitumor activity, addressing the challenges of treating solid tumors.

Each therapy is approved based on clinical endpoints such as overall survival, remission duration, or response rates, and each comes with its own risk–benefit profile that clinicians must consider when selecting the most appropriate therapy for a given patient.

Impact and Future Directions

Clinical Impact and Patient Outcomes
The approval of these immune cell therapies has dramatically altered the landscape of treatment for many cancers. Clinical studies have shown that these therapies can induce durable responses and, in some cases, long-term remissions even in patients with refractory disease. For instance, the introduction of CAR T‑cell therapies such as tisagenlecleucel and axicabtagene ciloleucel has resulted in unprecedented response rates in hematologic malignancies, leading to significant improvements in overall survival for patient groups that previously had very limited treatment options.

Moreover, the ability of these therapies to persist in the body—sometimes for years—provides not only immediate antitumor effects but also a form of “living drug” that offers memory and adaptability against tumor recurrence. The clinical impact is further underlined by the ability of Sipuleucel‑T to extend survival in prostate cancer patients in a setting where tumor shrinkage is not the primary clinical endpoint. These results emphasize an important shift in clinical trial endpoints from traditional tumor reduction to overall survival and quality of life measures.

Nonetheless, challenges remain. Adverse events such as cytokine release syndrome (CRS) and neurotoxicity associated with CAR T‑cell therapies require careful management and prompt intervention. There is also variability in patient responses and a fraction of patients who either do not respond or eventually relapse, which drives ongoing research into the mechanisms of resistance and the need for combination therapies or improved patient selection.

Future Trends and Research Directions
Looking forward, several important research directions are being pursued to enhance the utility, safety, and scope of immune cell therapies:

1. Expanding Indications:
Researchers continue to explore the use of these therapies in additional malignancies, especially solid tumors where challenges like the immunosuppressive tumor microenvironment have limited success until recently. With the recent approval of TIL-based therapy for melanoma (lifileucel), efforts are underway to adapt this strategy for other solid tumor types.

2. Combination Therapies:
Combining immune cell therapies with checkpoint inhibitors, targeted therapies, or even conventional chemotherapy could improve response rates and overcome resistance mechanisms. Early-phase clinical trials have shown that combination approaches may help in counteracting tumor escape while reducing individual treatment toxicities.

3. Personalized and Off-the-Shelf Products:
The future of immune cell therapy involves both personalization (tailoring treatments based on a patient’s specific tumor antigen profile and immune status) and the development of allogeneic “off-the-shelf” products. Such off-the-shelf approaches, including those derived from induced pluripotent stem cells (iPSCs), could reduce manufacturing time, lower costs, and broaden patient accessibility.

4. Technological Innovations:
Advances in gene editing and novel vector systems are expected to improve the safety and efficiency of cellular modifications. New approaches to monitor cell persistence and function (such as real-time imaging and improved potency assays) will likely lead to safer profiles and better clinical management of toxicities.

5. Biomarker-Driven Trials:
Identifying predictive biomarkers for cell therapy responses will be crucial. Understanding the interplay between tumor mutation burden, immune checkpoint expression, and T‑cell functionality can help stratify patients, ensuring that those most likely to benefit are selected for these expensive and intensive therapies.

6. Improved Manufacturing and Scalability:
One key challenge is the variability in manufacturing processes. Research and development activities aimed at scaling up production, standardizing cell processing, and reducing the heterogeneity among patient-derived products are essential to improve both safety and efficacy outcomes.

In summary, the clinical impact reflected in improved survival rates and durable responses is clear, yet ongoing research is required to address the limitations and broaden the application scope of immune cell therapies. The evolution from autologous to potential off-the-shelf products, the integration of combinatorial strategies, and the continuous refinement of regulatory frameworks indicate that innovation in this field is destined to accelerate further.

Conclusion
In conclusion, drawing on findings from reliable Synapse sources and current literature, there are currently seven FDA-approved immune cell therapies. These include Sipuleucel‑T (Provenge®), Tisagenlecleucel (Kymriah®), Axicabtagene ciloleucel (Yescarta®), Brexucabtagene autoleucel (Tecartus®), Idecabtagene vicleucel (Abecma®), Ciltacabtagene autoleucel (Carvykti®), and Lifileucel (Amtagvi®). This count reflects an evolving landscape where both hematologic and solid tumors benefit from tailored immunotherapeutic strategies.

The answer has first provided a broad introduction to immune cell therapies and their types and significance in modern medicine. It then detailed the FDA approval process—emphasizing the unique criteria for cell-based products such as potency assays, manufacturing consistency, and monitoring for long-term safety. Following this, a detailed list and description of the seven approved therapies were presented along with their specific indications and usage. Finally, the discussion broadened into clinical impacts, patient outcomes, future research directions, and the anticipated evolution of the field.

From a general perspective, these therapies have ushered in a new era of “living drugs” and have offered dramatic improvements in clinical outcomes for many patients. From a specific perspective, the seven FDA-approved products each address unique malignancies with distinct mechanisms and risk–benefit profiles. Yet, from a general-to-specific-to-general standpoint, the field is dynamic; while the current portfolio is seven, ongoing research into combination therapies, personalized products, and scalable manufacturing will doubtless expand—and further complicate—the regulatory and clinical landscape in the years to come.

In summary, as of today, based on the current evidence and regulatory approvals, there are seven immune cell therapies approved by the FDA. This number is expected to grow as research advances and new technologies refine the therapeutic landscape for both hematologic and solid malignancies.