Significant Positive Results Are Being Achieved in CAR-T and CAR-NK Cancer Treatments

The human immune system is a sophisticated and highly effective defense network, constantly working to protect the body from threats such as bacteria, viruses, and abnormal cells. Within this network are specialized cells that act as a security force, each with a distinct role. T cells, a specialized type of white blood cell, are trained to identify and eliminate individual threats with precision and efficiency. Another crucial component of this defense is a group of cells known as natural killer (NK) cells. These cells are equipped with an innate ability to recognize and destroy any cell that looks suspicious or damaged without needing prior training.

Despite this powerful natural defense, cancer cells are masters of disguise. They can develop mechanisms to evade immune surveillance, essentially becoming "invisible" to the T cells and NK cells trying to hunt them down. This ability to become immune-evasive is a fundamental challenge in cancer treatment. Even when the immune system recognizes a tumor, it may not have the right tools or a sufficient number of cells to overcome the cancer's defenses. This is why many traditional cancer treatments have focused on directly attacking the tumor, but this can cause significant damage to healthy cells as well.

This ability to become immune-evasive is a fundamental challenge in cancer treatment. Even when the immune system recognizes a tumor, it may not have the right tools or a sufficient number of cells to overcome the cancer's defenses. Traditional cancer treatments, focused on directly attacking the tumor, often cause significant damage to healthy cells as well.

The profound innovation of cellular immunotherapy, and specifically of Chimeric Antigen Receptor (CAR) therapies, is the development of a new approach: making the cancer visible again and empowering the body's own defense system to do the fighting. Once infused, these specially engineered cells have the ability to multiply to hundreds of millions, circulate throughout the body, and continue to hunt down any remaining cancer cells. This marks a new era in medicine where the treatment is not a drug that is cleared from the body, but a living, breathing force that can continue to work for years. The goal is to create a perpetual surveillance system that can prevent the cancer from ever returning.

A decade ago the idea of using the immune system as a cornerstone of cancer treatment was considered an exciting but niche area of research. Today it is one of the most transformative pillars of modern oncology. CAR-T and CAR-NK therapies (the T and NK correspond to the T and NK cells mentioned in the first paragraph above) transcend traditional methods like chemotherapy and radiation to offer highly personalized, "living medicines". CAR therapies, constructed using AI in labs, guide custom-made cells to targets and destroy them.

Each CAR molecule is a complex, lab-made protein that spans the immune cell's membrane, with a part of it extending outside and another part residing inside the cell. The external part, composed of fragments of synthetic antibodies, is the "GPS." It is specifically designed to bind to a unique protein, called an antigen, that is found on the surface of cancer cells. This binding mechanism is highly precise, allowing the engineered cell to latch onto one specific target. The internal part of the CAR transmits a signal that activates the immune cell to multiply and launch a lethal attack on the cancer cell it has identified. The precision of CARs allows immune cells to bypass the complex natural recognition processes that cancer cells have learned to evade. Researchers have continually refined the design of these CARs, with the field now exploring advanced generations of these molecules that incorporate additional features, such as the ability to produce helpful immune system signaling proteins, to make the cells even more powerful and resilient. This ongoing evolution highlights a broader trend: the focus of research is not just on finding new targets, but on making the very tool of therapy—the CAR—smarter, more effective, and more capable of overcoming the biological complexities of cancer.

The first time Emily Walsh, a 29-year-old with relapsed acute lymphoblastic leukemia (ALL), heard the term “CAR-T,” she thought it sounded like science fiction. She had already endured chemotherapy, radiation, and a stem cell transplant. Each time, her cancer returned. Her doctors told her the standard playbook was exhausted.

The CAR-T process was unlike anything she’d experienced. Doctors collected her own T cells, shipped them to a specialized lab, and genetically modified them to carry a chimeric antigen receptor (CAR) designed to target her leukemia. Weeks later, billions of reprogrammed T cells were infused back into her body.

The side effects were intense—fevers, chills, weeks in the hospital—but the results were extraordinary. Within a month, Emily’s bone marrow showed no detectable leukemia. She returned to teaching part-time, something she and her family had stopped daring to imagine.

CAR-T therapies like these have already changed the landscape for certain blood cancers. Clinical trials show complete remission rates of 70–90% in some relapsed leukemias and lymphomas. For patients who once faced certain death, these numbers represent hope of survival.

CAR-T cell treatment consists of four distinct steps:

1. Collection: The process begins with a procedure called leukapheresis, where a patient's blood is drawn through a vein and filtered to collect T cells. The rest of the blood is then returned to the patient. This process can be performed in one or more outpatient procedures, but for patients with rapidly progressing diseases, waiting for the cells to be manufactured can be a significant concern.

2. Engineering: The collected T cells are then sent to a specialized laboratory, often located far from the hospital, where they are genetically modified. This crucial step involves introducing the genetic instructions for the Chimeric Antigen Receptor (CAR) into the T cells.

3. Expansion: After being engineered, the new CAR-T cells are grown and multiplied in the laboratory until there are hundreds of millions of them. This process, from collection to completion, typically takes about 3 to 5 weeks, or sometimes up to two months, a period during which the patient's cancer could potentially progress.

4. Infusion: Once the living medicine is ready, the expanded CAR-T cells are shipped back to the hospital. The patient first receives a preparatory chemotherapy treatment to make their body more receptive to the new cells. The CAR-T cells are then infused back into the patient's bloodstream, much like a blood transfusion. Inside the body, the engineered T cells continue to multiply and begin their search-and-destroy mission against cancer cells bearing the target antigen. This personalized, meticulous process is one of the key reasons for the high cost and logistical complexity of CAR-T therapy, but it has yielded unprecedented results.

As of 2025, the U.S. Food and Drug Administration (FDA) has approved seven CAR-T cell therapies, each designed to target specific types of hematologic (blood) malignancies. The first of these therapies, Kymriah™ (tisagenlecleucel), was approved based on clinical trials that showed it could eliminate leukemia in the majority of children with relapsed acute lymphoblastic leukemia (ALL). Long-term studies have since demonstrated that many of these children have survived for years without their cancer returning. Since then, additional therapies have been approved for adults with blood cancers. These include Yescarta™ (axicabtagene ciloleucel) and Breyanzi™ (lisocabtagene maraleucel) for various lymphomas, as well as Tecartus™ (brexucabtagene autoleucel) for mantle cell lymphoma and adult ALL.15 In clinical trials for advanced follicular lymphoma, Yescarta was found to eliminate the cancer in nearly 80% of patients, with many remaining disease-free three years later.

Two CAR-Ts for multiple myeloma (cilta-cel / Carvykti and ide-cel / Abecma) are now allowed much earlier in treatment, after only 1–2 prior lines instead of many. That means patients can access them sooner, with better odds of benefit. The CD19 CAR-T Breyanzi now also covers chronic lymphocytic leukemia (CLL) and follicular lymphoma.

In a significant advancement, the FDA approved a new therapy, Aucatzyl™ (obecabtagene autoleucel), in November 2024 for adults with relapsed or refractory B-cell precursor ALL. The approval was based on trial results where 42% of patients achieved a complete response within three months. These treatments have been described as transformative for patients with advanced cancers that were not controlled by other standard treatments. The durability of these responses, with more than 30% of participants in trials for large cell lymphoma alive without any evidence of cancer five years after treatment, provides compelling evidence that CAR-T can offer the potential for lasting remissions, or even "apparent cures," in a patient population with very few other options.

The limitations of current therapies have prompted researchers to develop new and more intelligent CARs. One of the most promising strategies is the development of multi-target CARs which may prevent the cancer from escaping immune surveillance by simply shedding one of its target antigens. In a trial to treat glioblastoma, a notoriously aggressive brain cancer, a dual-target CAR-T therapy, targeted not one but two proteins—epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The trial combined a regimen of NK cell therapy with the immune-boosting agent, and achieved 100% disease control in a small cohort of five patients. Notably, three of the patients responded to the treatment, with two of them achieving a near-complete response, which is meaningful in such a tough disease.

Solid tumors—like breast, lung, and colon cancers—present a tougher problem.

• They have a protective "fortress": A barrier of other cells that makes it hard for CAR-T cells to get in.

• The environment is toxic: The area around a tumor is low in oxygen and nutrients, which exhausts and kills the CAR-T cells.

• The targets are tricky. The proteins on solid tumor cells often look very similar to those on healthy cells, leading to dangerous side effects.

Nevertheless, there is progress. Researchers started testing a "switchable" CAR-T that can be turned on and off to reduce side effects. A trial has been launched for metastatic breast cancer. A clinical trial for neuroendocrine tumors (NETs) has shown early signs of efficacy, including a patient with stable disease and a 12% tumor shrinkage. The trial has successfully advanced to a higher dose, signaling positive progress and no major safety concerns. Small-scale clinical trials are also underway for a variety of other solid tumors, including ovarian, colorectal, breast, and prostate cancers. The field is maturing, moving from a single-target, one-size-fits-all approach to a more sophisticated, multi-faceted strategy to overcome the biological complexities of solid tumors.

What’s next in CAR-T

• In-body CAR-T: Scientists at Stanford showed it's possible to make CAR-T cells directly inside the body using techniques similar to mRNA vaccines. This worked well in mice and could make the treatment easier and cheaper, avoiding the need to remove and modify cells in a lab. Early human tests just started.

• Smarter “logic-gated” CAR-Ts: These are designed like switches — only attacking cells with the right combination of signals, so they hit cancer but spare normal tissue.

• Off-the-shelf CAR-Ts: The idea is to make CAR-T products from healthy donors, freeze them, and use them like standard drugs. Still in early stages, but could make treatment faster and cheaper.

Overall, the focus is on expanding CAR-T to solid tumors (like brain or breast cancer), reducing side effects, and making it work for more people, with many trials showing quick improvements in tough cases.

In addition to trials in CAR-T therapies, CAR-NK research is showing major promise. NK cells possess several unique advantages that make them a promising foundation for the next generation of cellular immunotherapy. Unlike T cells, natural killer (NK) cells are part of the existing immune system. They are generalists, programmed by evolution to recognize stressed or abnormal cells without requiring prior exposure. They have an innate intelligence; they can recognize and destroy cancer cells without needing prior exposure or activation, a capability referred to as "natural cytotoxicity". This built-in killing ability makes them a powerful tool. Furthermore, arming NK cells with a CAR adds a layer of refined precision to their already potent anti-cancer activity.

Also, CAR-NK therapy has a significantly more favorable safety profile compared to CAR-T. CAR-NK posing a much lower risk of inducing severe side effects such as Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Finally, CAR-NK cells offer a crucial solution to one of CAR-T's biggest logistical challenges. Because they lack a specific T cell receptor, NK cells do not cause Graft-versus-Host Disease (GvHD) when transferred between different individuals. This fundamental biological difference means that CAR-NK therapies can be manufactured using cells from a universal donor, making them a suitable candidate for "off-the-shelf" products. The superior safety profile of CAR-NK is not coincidental; it is a direct consequence of the unique biology of NK cells, which allows them to bypass the major safety hurdles inherent in CAR-T therapy.

There are now about 50 ongoing trials testing CAR-NK for various cancers. At MD Anderson Cancer Center, a pioneering trial infused patients with CAR-NK cells derived not from the patients themselves, but from umbilical cord blood donors. This was a key difference: CAR-T requires weeks of custom manufacturing, while CAR-NK could potentially be an off-the-shelf therapy, ready in days and manufactured in large batches. These mass-produced cells can then be stored and made readily available to treat multiple patients as needed. This scalable approach directly addresses the major problems associated with CAR-T's individualized manufacturing, which is both time-consuming and incredibly expensive, often costing hundreds of thousands of dollars for a single treatment. The long manufacturing time for CAR-T can be a critical drawback for patients with aggressive, fast-progressing cancers, for whom a delay of weeks could be detrimental.

At the Annual Meeting of the American Association for Cancer Research (AACR) held in April 2025, trial results for a CAR-NK therapy with "logic gates" (built-in rules to attack only cancer cells) were presented indicating complete remissions in some patients with relapsed blood cancers.

The ability to create a simpler, more affordable, and scalable product is not just a logistical advantage; it has the potential to democratize this revolutionary treatment, making it a viable option for a wider population and in a greater variety of healthcare settings.

The central challenge of current research is combining the proven persistence and efficacy of CAR-T with the increased safety and lower cost of CAR-NK. Research is also combining CAR-T and CAR-NK with engineered immune cells that are programmed with checkpoint inhibitors, and even designing cancer vaccines that prime the immune system before cell therapy. In addition, combining CAR-NK with tiny particles (nanoparticles) is moving into early human trials.

Here’s a side-by-side comparison:

At Dana-Farber, Dr. Catherine Wu’s team has developed personalized vaccines that train T cells to recognize unique tumor neoantigens. Early trials in melanoma showed patients mounting durable immune responses, some remaining cancer-free years later. AI plays a crucial role here—scanning each patient’s genome, identifying the most promising targets, and simulating which neoantigens the immune system is most likely to attack. What once took months can now be done in days.

Meanwhile, companies like Kite Pharma, Novartis, and Fate Therapeutics are running large-scale trials of CAR-NK and “armored CAR-T” cells—engineered not only to target cancer but to resist suppression by the tumor environment.

Why AI Matters Here

AI is woven into every stage of these therapies. Machine learning helps:

• Identify which tumor markers make the best targets.

• Model how engineered cells will behave in the complex tumor ecosystem.

• Predict which patients are most likely to respond—or experience severe side effects.

• Streamline manufacturing, reducing time from biopsy to infusion.

In some labs, AI models now simulate entire “digital twins” of a patient’s immune system, testing thousands of possible CAR designs in silico before moving forward with real cells.

A Patient’s View

For Emily, the former teacher in remission from ALL, the details of receptors and vectors mattered less than the outcome. “They took my cells out, re-trained them, and sent them back to fight for me,” she says. “It feels like I’ve been given my own army.”

Her story—and those of hundreds of others—underscores both the promise and the unfinished work. CAR-T and CAR-NK are not panaceas. Relapse still happens. Access remains limited. Costs are staggering. But the fact remains: patients once out of options are alive today because of these living medicines.

The New Frontier

Dr. Carl June, one of the pioneers of CAR-T therapy at the University of Pennsylvania, describes the moment bluntly: “We’re at the Wright Brothers stage of cell therapy. We’ve shown it can fly. Now we need to make it safe, reliable, and available to everyone.”

That journey is underway. With AI accelerating discovery and logistics, with immunology pushing boundaries, and with patients demanding access, CAR-T and CAR-NK therapies are carving out a new frontier.

Not every patient will be saved. But more than ever before, the immune system itself—rewired by AI and biotechnology—is becoming one of medicine’s most powerful weapons against cancer.

Some of the most innovative research is moving beyond the principles of immunotherapy entirely. A recent study published in Nature introduced a radically different approach: the AUN bacteria cancer treatment, which operates independently of the immune system. Preclinical trials for AUN therapy have shown tumor destruction with minimal side effects and no signs of Cytokine Release Syndrome (CRS), a significant advantage over many immunotherapies. While still in the very early stages of development with clinical trials expected to begin within six years, this discovery challenges 150 years of assumptions about how to fight cancer and offers a lifeline to a previously underserved patient population.

Trials in other bacteria-based cancer treatments are ongoing. Here are some of the most promising results as of September 1, 2025:

• Clostridium novyi-NT: Demonstrated real tumor destruction in humans (necrosis and partial shrinkage), though with safety/tolerability issues.

• CRS-207 (Listeria-mesothelin): Showed improved survival in pancreatic cancer and strong disease control in mesothelioma, making it the most clinically encouraging bacteria-based therapy to date.

• Salmonella TAPET-CD / VNP20009 & JNJ-64041757: Validated tumor-homing and safety, but clinical benefits were modest compared to the above.

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If you are dealing with a life-threatening disease, and want to know the latest in how medical science is addressing that disease, feel free to contact me for a no cost, obligation free consultation.

rod@emergingcures.org