ImmunityBio is a biotechnology company built around a single core idea: that stimulating the body’s own immune cells, particularly natural killer cells and certain T cells, can fight both cancer and chronic infections. Its lead drug, Anktiva (known in research as N-803), is an engineered form of the immune signaling molecule IL-15 and became the first IL-15-based therapy to receive FDA approval when it was cleared in April 2024 for a specific type of bladder cancer. But the company’s ambitions stretch well beyond one cancer type, spanning lung cancer combination therapies, off-the-shelf natural killer cell products, an HIV cure strategy, and a modified adenovirus vaccine platform.
What IL-15 Does and Why ImmunityBio Engineered a Stronger Version
IL-15 is a naturally occurring immune signaling protein that drives the growth and activation of two cell types the body relies on to destroy abnormal or infected cells: CD8+ T cells (the “killer” T cells) and natural killer (NK) cells. In its natural form, IL-15 clears from the bloodstream quickly and is difficult to use as a drug. ImmunityBio’s solution was to create a superagonist complex, a modified version of IL-15 that is pre-bound to part of its own receptor and fused to a fragment that extends how long it circulates. The result is a molecule that activates the same immune pathways as natural IL-15 but does so more potently and for longer.
Anktiva works by binding to IL-15 receptors on CD4+ and CD8+ T cells as well as NK cells, stimulating their growth and activity while avoiding the expansion of regulatory T cells, which are the immune cells that normally dial down immune responses.1PubMed Central. Transforming non-muscle invasive bladder cancer (NMIBC) treatment: FDA approval of Anktiva in combination with BCG That distinction matters: many cancer immunotherapies struggle because they fire up the immune system broadly, including the very cells that suppress the anti-tumor attack. By selectively boosting the offensive arm of immunity while leaving the brakes alone, the drug aims to tip the balance toward tumor destruction.
In preclinical tumor models, N-803 produced significant immune activation through what researchers call a Th1 response, the branch of the immune system associated with fighting tumors and intracellular infections, and its tumor-suppressive effects were primarily driven by NK and CD8+ T cells.2PubMed Central. Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies This dual-cell mechanism is central to nearly everything ImmunityBio does, whether the target is a solid tumor, a blood cancer, or a virus hiding inside immune cells.
Bladder Cancer and the First FDA Approval
The condition that brought Anktiva to market is non-muscle invasive bladder cancer (NMIBC) that no longer responds to BCG, the tuberculosis vaccine repurposed decades ago as a bladder cancer treatment. BCG is instilled directly into the bladder and works by provoking a local immune response against cancer cells. It remains the standard first-line therapy, but a meaningful fraction of patients eventually stop responding. For those patients, the traditional next step has been surgical removal of the bladder, a major operation with lifelong consequences.
The QUILT-3.032 trial tested Anktiva combined with BCG in these BCG-unresponsive patients who had carcinoma in situ (CIS), the flat, high-grade form of the disease. The treatment involved one instillation per week for six weeks. Among 77 patients evaluated for efficacy, about 62% achieved a complete response. Of those responders, roughly 58% remained free of NMIBC for more than 12 months, and about 40% stayed disease-free at 24 months. Among responders, 90% avoided cystectomy, with an 89% probability of remaining cystectomy-free at two years and 100% bladder cancer-specific survival at that time point.3PubMed Central. Therapeutic Advances in Bladder Preservation for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer – Section: New FDA-Approved Intravesical Gene and Immunotherapies for BCG-Unresponsive NMIBC
Those numbers earned Anktiva its FDA approval in April 2024 as an immunotherapy for BCG-unresponsive NMIBC with CIS, with or without papillary tumors. For bladder cancer patients who had exhausted their standard options, this represented the first time an IL-15 superagonist had been approved for any indication. The practical value is straightforward: patients who respond can keep their bladders and avoid the surgical, urinary, and quality-of-life burdens of cystectomy.
Pairing with Checkpoint Inhibitors in Lung Cancer
Checkpoint inhibitors like nivolumab (a PD-1 blocker) and drugs targeting PD-L1 have transformed treatment for several cancers, but a large share of patients either do not respond or eventually relapse. ImmunityBio’s hypothesis is that N-803 can prime the immune system in ways that make checkpoint inhibitors work better, and early data suggest this combination has legs.
In preclinical models of metastatic breast cancer and colon cancer, N-803 combined with an anti-PD-L1 antibody reduced lung metastases and tumor burden more than either drug alone, and extended survival. The combination’s effectiveness depended on both CD8+ T cells and NK cells, and was associated with increased numbers of these activated immune cells at the site of metastasis and in the spleen. The anti-PD-L1 component specifically enhanced the killing capacity of CD8+ T cells beyond what N-803 achieved on its own, as measured by increased production of granzyme B and interferon-gamma, the molecular tools these cells use to destroy tumors.4PubMed Central. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy
That preclinical rationale carried into clinical testing. A phase 1b trial combined ALT-803 (the earlier name for N-803) with nivolumab in patients with advanced non-small cell lung cancer (NSCLC) who had already progressed on PD-1 therapy. The trial reported promising clinical activity, showing evidence of anti-tumor responses in patients whose disease had become refractory to nivolumab alone.5The Lancet Oncology. Phase 1b trial of ALT-803, an IL-15 superagonist, with nivolumab in patients with advanced non-small-cell lung cancer – Section: Interpretation Multiple clinical studies across different cancer types have since confirmed that N-803 can be safely combined with nivolumab and that the pairing produces encouraging responses even in patients whose cancers had stopped responding to checkpoint blockade alone.2PubMed Central. Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies
This is a meaningful finding because checkpoint inhibitor resistance is one of the biggest unsolved problems in oncology. If N-803 can rescue responses in patients whose tumors have figured out how to evade PD-1 or PD-L1 blockade, it opens a second chance at durable control for a large group of people who currently have few good options.
Engineered Natural Killer Cells as Off-the-Shelf Therapies
Beyond Anktiva itself, ImmunityBio has invested heavily in cell-based therapies using natural killer cells. Unlike CAR-T cell therapies, which require harvesting and engineering a patient’s own T cells (a process that takes weeks and costs hundreds of thousands of dollars), NK cell products derived from established cell lines can be manufactured in advance and given to any patient without immune matching. This “off-the-shelf” approach could dramatically reduce cost and time to treatment.
The NK-92 cell line, originally isolated from a patient with lymphoma, has been successfully modified to express a high-affinity version of the CD16 receptor, which lets NK cells grab onto antibodies already coating a tumor cell and kill it through a process called antibody-dependent cellular cytotoxicity. The same cells can also be armed with chimeric antigen receptors (CARs) that recognize specific proteins on tumor surfaces and trigger NK cell activation directly.6PubMed Central. The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy
One product in this family, PD-L1 t-haNK (targeted high-affinity NK), is engineered to specifically recognize PD-L1, a protein that many tumors use to hide from the immune system. In laboratory testing, irradiated PD-L1 t-haNK cells killed all 20 human cancer cell lines tested, spanning triple-negative breast cancer, lung, urogenital, and gastric cancers. Their killing ability correlated with how much PD-L1 the tumor cells expressed, and pretreating tumor cells with interferon-gamma (which upregulates PD-L1) made the engineered NK cells even more effective.7PubMed Central. PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations The irony is elegant: a molecule that tumors exploit for immune evasion becomes the very target that attracts the engineered killer cell.
The synergy between engineered NK cells and N-803 has also been tested directly. In a neuroblastoma model, CAR-NK cells targeting a protein called ROR1 showed significantly improved tumor killing when combined with N-803. The combination enhanced survival in mice bearing human neuroblastoma tumors compared to CAR-NK cells alone, and boosted the release of key effector molecules like granzyme B, interferon-gamma, and perforin from the NK cells.8Molecular Therapy: Oncology. Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts This supports the broader strategy of using Anktiva not just as a standalone drug but as a booster that enhances the performance of cell-based therapies.
An HIV Cure Strategy Built on the Same Immune Activation
The same immune-activating properties that make N-803 useful against cancer have opened a parallel line of research in HIV. The central challenge in curing HIV is the viral reservoir: HIV inserts its genetic material into long-lived memory CD4+ T cells and goes dormant, invisible to the immune system and untouched by antiretroviral drugs. Even patients who have been on antiretroviral therapy (ART) for decades still carry this hidden reservoir, and the virus rebounds if treatment is stopped.
ImmunityBio’s approach applies what researchers call a “kick and kill” strategy. N-803 stimulates latent HIV to begin replicating inside those dormant memory cells (the “kick”), which forces the previously hidden infected cells to reveal themselves. The activated NK cells and CD8+ T cells, also revved up by N-803, then recognize and destroy the exposed cells (the “kill”). The goal is to shrink the viral reservoir enough that the immune system can maintain control without lifelong ART.
The most striking evidence for this approach comes from a study in macaques infected with SHIV (a laboratory hybrid of HIV and SIV). Animals on ART-suppressed infection were treated with N-803 combined with broadly neutralizing antibodies (bNAbs). The treatment induced immune activation and brief bursts of detectable virus, though only limited reductions in the reservoir were measured during the treatment period. The real test came when ART was stopped: viral rebound occurred in all animals initially, but roughly 70% of the macaques treated with the N-803 plus antibody combination then achieved durable viral control without any further antiretroviral drugs.9PubMed Central. Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques
A 70% rate of sustained viral control after stopping ART is a remarkable result in primate research, though it comes with caveats. SHIV is not identical to HIV-1, macaque immune systems differ from human ones in relevant ways, and the broadly neutralizing antibodies used in this study are themselves complex biologics still being refined for clinical use. Still, the finding represents one of the most promising preclinical results in the HIV cure field and has prompted clinical trials to test whether the same approach works in people.
A Modified Adenovirus Vaccine Platform
ImmunityBio’s infectious disease work extends beyond HIV treatment to vaccine development, built on a modified adenovirus vector. Adenovirus type 5 (Ad5) has long been an attractive vehicle for delivering vaccine antigens because it reliably provokes strong immune responses. The problem is that most adults have already been infected with Ad5 at some point in their lives, and their pre-existing immunity to the virus itself blunts the vaccine’s effectiveness, essentially shooting down the delivery truck before it can unload its cargo.
To get around this, ImmunityBio developed a second-generation Ad5 vector with additional gene deletions (E1, E2b, and E3 regions removed). Preclinical testing showed that these modified vectors remained potent immune stimulators even in animals with significant pre-existing Ad5 immunity, a problem that crippled first-generation Ad5 vectors with only the E1 region deleted.10PubMed Central. Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity This platform has been applied to vaccine candidates targeting several pathogens, including SARS-CoV-2 during the COVID-19 pandemic.
The rationale for a T-cell-focused vaccine is distinct from the antibody-focused approach used by the mRNA COVID-19 vaccines. While antibodies can be evaded by viral mutations in surface proteins, T-cell responses tend to target more conserved parts of the virus that are harder to mutate away. A vaccine that generates strong T-cell memory could provide more durable cross-variant protection, at least in theory. Whether this translates into meaningful clinical advantages over existing vaccines is still being evaluated, but the platform itself has proven versatile enough to accommodate multiple pathogen targets.
Safety Profile and How Anktiva Is Given
For a drug designed to aggressively stimulate the immune system, safety is an obvious concern. Overstimulation could trigger autoimmune-like toxicity or dangerous inflammatory cascades. The clinical experience with N-803 so far has been relatively reassuring, though not without caveats.
In the bladder cancer setting, Anktiva is given by intravesical instillation, meaning it is delivered directly into the bladder through a catheter. This local delivery limits systemic exposure and keeps most of the immune activation confined to the organ where the cancer lives. In other trials, N-803 has been administered subcutaneously (injected under the skin). A phase 2 trial testing N-803 as maintenance therapy after allogeneic stem cell transplant in patients with acute myeloid leukemia or myelodysplastic syndrome found that the most common adverse events were self-limited injection site skin rashes. One week after dosing, the researchers observed enhanced NK cell proliferation and improved anti-tumor killing without signs of immune exhaustion. Five patients developed acute graft-versus-host disease after N-803 administration, though all responded promptly to steroids, and four patients developed chronic graft-versus-host disease.11Transplant and Cellular Therapy. N-803, an IL-15 Superagonist Complex as Maintenance Therapy After Allogeneic Donor Stem Cell Transplant for Acute Myeloid Leukemia or Myelodysplastic Syndrome; A Phase 2 Trial
The graft-versus-host disease finding is worth understanding in context. In the transplant setting, the immune system being boosted partly belongs to the donor, and there is always a baseline risk that activated donor immune cells will attack the recipient’s tissues. The fact that N-803 could exacerbate this is not surprising given its mechanism, and the cases were manageable. Outside of the transplant setting, graft-versus-host disease is not a relevant concern. The injection site reactions and transient flu-like symptoms reported across trials are consistent with what you would expect from a potent immune stimulant and have generally not been treatment-limiting.
Where the Platform Stands in the Broader Immunotherapy Landscape
ImmunityBio operates in a crowded field. Checkpoint inhibitors from companies like Merck, Bristol Myers Squibb, and Roche dominate cancer immunotherapy revenue. CAR-T therapies from Novartis and Gilead/Kite have established the cell therapy market for blood cancers. Gene therapy approaches to bladder cancer from other companies are also competing for the BCG-unresponsive NMIBC space.
What makes ImmunityBio’s approach distinctive is less about any single product and more about the connective tissue between its programs. The IL-15 superagonist is not just a drug; it functions as a platform amplifier. It enhances checkpoint inhibitor responses in lung cancer. It boosts engineered NK cell killing in neuroblastoma. It flushes out latent HIV. It could, in theory, improve the performance of any immunotherapy that depends on NK cells or CD8+ T cells. Whether that versatility translates into commercial success depends on how well the clinical data hold up in larger, randomized trials across multiple indications, but the scientific logic of amplifying the body’s existing killer cells remains compelling. The company’s challenge now is execution: manufacturing NK cell products at scale, running the late-stage trials needed to expand Anktiva’s label beyond bladder cancer, and demonstrating that the HIV cure strategy works in humans as well as it did in macaques.