Natural Killer (NK) Cell Therapeutics Market

Market Overview

The global natural killer (NK) cell therapeutics market size was worth USD 92 million in 2022 and is estimated to reach an expected value of USD 3,160 million by 2031, growing at a CAGR of 44.3% during the forecast period (2022–2031).

The increasing interest of the pharmaceutical industry in cellular immunotherapy potential has been a catalyst for progress in the global NK cell therapeutics market. The pharmaceutical industry is currently dominated by other immunotherapies such as CAR T-cell therapies, checkpoint inhibitors, and cytokines. However, the proportion of natural killer (NK) cell therapeutics is anticipated to increase, given the ability to fulfill unmet medical needs, overcome limitations associated with existing immunotherapies, and address complex, challenging targets. The NK cell therapies provide several advantages, such as antigen non-specificity, easy isolation and ex vivo expansion, and minimal production cost. The recent increase in approvals received for cancer immunotherapies is considered to have added value to the NK cell therapeutic development.

Highlights

• The NK cell therapy (unmodified) dominates the natural killer (NK) cell therapy type segment
• The MG4101 dominates the pipeline product segment
• The relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) dominates the indication segment
• North America is the highest contributor to the market

Market Dynamics

Market Drivers

Rising Number of Clinical Trials

There are many emerging therapies concerning natural killer (NK) cell therapies, such as CAR T-cell therapy. But considering the safety, cost, and efficacy, many biopharmaceutical companies are trying to create NK cell therapy-based products with fewer adverse effects than other immunotherapies. Manufacturing cost is low, and there is a vast range of applications, including COVID-19. Therefore, the focus of the companies is shifting toward NK cell therapies. Hence, companies are investing and focusing on creating such product candidates. The number of clinical developments is also increasing due to massive competition between established and emerging companies. For instance, major players, such as Fate Therapeutics Inc., Cytovac A/S, Celularity Inc., and Sanofi S.A., are strengthening the Company's product portfolio concerning NK cell therapeutics. The increasing number of trials by significant players in the global NK cell therapeutics market reflects the ongoing effort of the companies on numerous clinical trials that would lead to approvals from the regulatory bodies, hence, would aid in the growth of the global NK cell therapeutics market at a favorable rate.

Increasing Incidence and Prevalence of Cancer

Cancer is the primary application of NK cell therapy, and NK cells are essential to tumor immunosurveillance. The global prevalence of cancer is rising due to factors such as the growing geriatric population, sedentary lifestyle, and other risk factors imposing a combinatorial impact. While incidence rates continue to spike, primarily due to high-fidelity diagnostic and screening measures, cancer prevalence has also been a significant concern for the global healthcare industry. According to the World Health Organization (WHO), cancer is the second leading cause of death across the globe and accounted for an estimated 10 million patient deaths in 2020.

The rising cancer cases are observed due to tobacco use, alcohol consumption, and lack of physical activity. According to the American Cancer Society, in 2021, there were ~1.9 million new cancer cases diagnosed and 608,570 cancer deaths in the U.S. NK cell therapies are very useful in detecting and killing tumor cells with more safety and fewer side effects; therefore, many companies have an immense pipeline product portfolio in regard with NK cell therapy. Due to the increase in cancer cases, demand for NK cell therapies will increase shortly, eventually accelerating the growth of the global NK cell therapeutics market.

Market Restraint

Lack of Specificity and Poor In-Vivo Survival of the NK Cells

Natural killer (NK) cells recognize targets stressed by malignant infection and are long-lived. They become attentive by interacting with major histocompatibility antigen (MHC) class I molecules, thus producing cytokines. The persistence and in vivo expansion of NK cells depend on lymphodepletion chemotherapy to release the endogenous IL-15. Cytokines are also responsible for enhancing in vivo expansion; nevertheless, IL-2 has the downside of stimulating CD25High regulatory T-cells (Tregs), which limits their efficacy and persistence. Due to low in vivo persistence, it is difficult to permeate into the solid tumor sites, along with suppression from the tumor microenvironment (TME). Also, being considered a component of innate immune defense, sometimes NK cell lacks antigen-specific cell-surface receptors, thus missing out on attacking the target cell. As a result of these challenges, there could be a significant impact on the global NK cell therapeutics market.

Market Opportunities

Rising Number of Partnerships and Collaborations

The number of partnerships and collaborations in the medicinal field has made abrupt changes in the healthcare system. Biopharmaceutical companies are trying to match themselves with new technologies to improve the overall design from drug discovery to drug commercialization. The key players in the global NK cell therapeutics market are partnering and collaborating with emerging companies to develop novel targeted therapies. These opportunities will drive the global NK cell therapeutics market to grow significantly in the coming years.

Regional Analysis

North America Dominates the Global Market

Based on region, the global natural killer NK cell therapeutics market is analyzed across North America, Europe, and Asia-Pacific. 

North America is the highest revenue contributor and is estimated to exhibit a CAGR of 38.8% during the forecast period. High costs associated with CAR T-cell therapies, unmet clinical needs related to existing therapeutic options for target indications, and ongoing success in developing NK cells as therapeutics are likely to contribute to the growth of NK cell therapeutics during the forecast period. Additionally, established U.S.-based biopharmaceutical companies are forming alliances or collaborating with emerging companies to enhance their research in the U.S. For instance, in June 2021, Gilead Sciences, Inc. collaborated with Shoreline Biosciences, Inc. to develop NK cell therapies from induced pluripotent stem cells (iPSC). In April 2020, Janssen Biotech, Inc. collaborated with Fate Therapeutics, Inc. to support the Company's iPSC product platform and Janssen's exclusive tumor-targeting antigen binders for the development of novel chimeric antigen receptor CAR-NK product candidates to treat hematologic malignancies and solid tumors. These factors will likely propel the U.S. NK cell therapeutics market over the forecast period.

Europe is anticipated to grow at a CAGR of 74.5% during the forecast period. According to the journal Cancer Medicine, in Germany, nearly 20% of women and 25% of men die of cancer, and it is expected that approximately 43% of women and 51% of men are likely to develop cancer during their lifetime. Thus, the growing incidence of target indications and cost-effective treatment options will likely contribute to the market's growth during the forecast period.

Asia-Pacific and Japan is the third largest region. According to the European Journal of Clinical Nutrition, cancer has been Japan's leading cause of death since 1981. In 2018, approximately 27.00% of total deaths in Japan were due to cancer. The increasing incidence of target indications coupled with the rising number of relapsed or refractory cases showing response failure to alternative treatments has created the need for novel therapies in the country, which is anticipated to propel the growth of the overall NK cell therapeutics market in Japan. Moreover, the Ministry of Health, Labour, and Welfare (MHLW) plays a vital role in taking the initiative to develop novel drugs in Japan.

Several active steps have also been laid out by the government of Japan and other nongovernmental organizations that are fuelling the growth of this market. Approximately 40% of the top pharmaceutical companies in Asia-Pacific are based in Japan. The growing pharmaceutical research and development expenditure is expected to support the development of novel NK cell therapies for treating patients with cancer and infectious diseases.

Segmental Analysis

The global natural killer (NK) cell therapeutics market is segmented by natural killer (NK) cell therapy type, pipeline product, indication, and region. 

Based on the natural killer (NK) cell therapy type, the global (NK) cell therapeutics market has been divided into NK cell therapy (unmodified), CAR-NK cell therapy (modified), and NK cell engager. 

The NK cell therapy (unmodified) segment dominates the global market and is estimated to exhibit a CAGR of 57.6% during the forecast period. NK cells observe targets stressed by malignant transformation and infection and can be long-lived. They become attentive when interaction with significant histocompatibility antigen (MHC) class I occurs and gain the function to kill targets, producing cytokines. There are two types of NK cell therapies, i.e., allogeneic and autologous. In autologous, the donor is the person, whereas in allogeneic, the donor is another healthy individual.

By pipeline product, the global NK cell therapeutics market is segmented into AFM13, MG4101, GTA002 (oNKordA), and TAK-007. 

The MG4101 segment owns the highest market share and is estimated to exhibit a CAGR of 36.2% during the forecast period. MG4101 is an off-the-shelf NK cell therapy (unmodified) treatment developed by GC Cell (GC Biopharma corp.). MG4101 is an allogeneic and cytotoxic natural killer (NK) cell therapy derived from a healthy donor's normal cells. These normal or healthy cells are collected via the leukapheresis process, which is then ex vivo expanded and cryopreserved for patient utilization. MG4101 has completed a phase II study in patients with hepatocellular carcinoma (HCC). The trial evaluated the safety and efficacy of MG4101 in patients with HCC and was conducted in South Korea. Furthermore, the product was investigated as a pilot study of MG4101 for patients with relapsed or refractory acute myeloid leukemia. MG4101 was also examined in a phase I combination trial with rituximab for patients with relapsed or refractory non-Hodgkin's lymphoma, which further enhances the revenue growth of MG4101 in multiple indications of cancer in years to come.

By indication, the global NK cell therapeutics market has been segmented into hepatocellular carcinoma (HCC), acute myeloid leukemia (AML), relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL), and peripheral T-cell lymphoma (PTCL).

The relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) segment is the highest contributor to the market. Non-Hodgkin's lymphoma (NHL) is a cancerous tumor in the lymphoid tissues, primarily the lymph nodes. Follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, and primary CNS lymphoma are the most common adult B-cell lymphoma. The treatment for NHL is highly variable, depending on the stage, grade, and type of lymphoma, as well as a variety of patient variables. For many years, surgical resection, chemotherapy, and radiotherapy were the only cancer treatments accessible. Immune checkpoint inhibitors and adoptive cell treatments have recently emerged as intriguing options. Recent breakthroughs in cellular therapies and immunotherapies imply that attacking tumors with an activated immune system can overcome chemo-resistance. Early clinical experience with these techniques has generated impressive therapeutic results. These cancer immunotherapies work by assisting the patient's immune system to recognize and eliminate cancer cells.

Recent Developments

• February 2023- Dr. Karim Chamie, Associate Professor of Urology at UCLA, presented "Quality of life in QUILT 3.032 study: Patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) receiving IL-15RFc superagonist N-803 plus BCG" at the ASCO Genitourinary Cancers Symposium (ASCO GU) conference in San Francisco from February 16 to 18, according to ImmunityBio, Inc. (NASDAQ: IBRX), a clinical The Biologics License Application (BLA) for ImmunityBio's N-803 with BCG for the treatment of NMIBC CIS with a Prescription Drug User Fee Act (PDUFA) date of May 23, 2023, is currently being reviewed by the Food and Drug Administration (FDA).
• February 2023- Clinical-stage immunotherapy firm ImmunityBio, Inc. said it had completed funding to increase operating cash and support its ongoing business activities. With several institutional investors, the Company entered into a securities purchase agreement for a registered direct offering that called for the issuance of ImmunityBio common stock and warrants to buy additional shares of the Company's common stock. Subject to customary closing conditions, this transaction is anticipated to generate gross proceeds at closing of about USD 50 million before offering-related costs. The warrants generate up to USD 60 million in extra gross profits if fully exercised.