LAG-3-Next Generation Immunotherapy-Competitive Landscape and Market Forecast-2035
DelveInsight's 'LAG-3-Next Generation Immunotherapy-Competitive Landscape and Market Forecast-2035' report delivers an in-depth understanding of the LAG-3 as well as the market trends of LAG-3-Next Generation Immunotherapy in the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan.
The report provides the upcoming drugs, market share of this target by indications, forecasted market size of LAG-3-Next Generation Immunotherapy from 2022 to 2035 segmented by seven major markets. This report discusses the recent findings on LAG-3, the role it plays in regulating immune responses in different cell types and the rationale for targeting LAG-3 for effective cancer immunotherapy. The report also covers the current scenario, market drivers, market barriers and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.
Study Period: 2022-2035.
Cancer immunotherapy (CI) is rapidly advancing and can now be considered to be the "fifth pillar" of cancer therapy, joining the ranks of surgery, cytotoxic chemotherapy, radiation, and targeted therapy. The CI which has sparked the most interest involves antibodies to inhibitory immune checkpoint molecules. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade.
Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation, and growth. T cells are a type of white blood cell that are part of the immune system. Activation of cytotoxic T cells by antigens enables them to kill unhealthy or foreign cells. It binds MHCII molecules and modulates T-cell function than either CTLA-4 or PD-1. It acts by regulating CD8+ Tcell expansion in immune reactions that have already been initiated (inhibitory signal) and also, by increasing the Treg cell activity.
The inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.
LAG-3 is a transmembrane protein with structural homology to CD4, in which it includes four extracellular IgG domains. The membrane-distal IgG domain contains a short amino acid sequence, the so-called extra loop that is not found in other IgG superfamily proteins. The intracellular domain contains a unique amino acid sequence (KIEELE) that is required for LAG-3 to exert a negative effect on T cell function. LAG-3 can be cleaved at the connecting peptide (CP) by metalloproteases to generate a soluble form, which is detectable in serum
After a T cell is activated to kill its target cell, LAG-3 expression is increased to turn off the immune response, so that the T cell does not go on to attack healthy cells. Inhibition of the immune response is accomplished through the binding of LAG-3 to an antigen-presenting complex called MHC II, which together signal the T cell to stop activation and multiplication.
However, in certain situations where T cells experience prolonged exposure to an antigen, such as cancer or chronic infection, the T cells become desensitized and lose their ability to activate and multiply in the presence of the antigen.
Preclinical studies suggest that targeting the LAG-3 pathway in combination with other potentially complementary immune pathways may be a key strategy to more effectively activate the antitumor immune response.
Beyond the inhibitory activity of LAG-3 on different types of lymphocytes, LAG-3 may also be necessary to negativelyregulate autoimmunity in many disease-prone environments. For instance, loss of LAG-3 substantially can accelerate type 1 diabetes in Non-Obese Diabetic (NOD) mice with 100% incidence. LAG-3 deficient mice can exhibit increased antigen-reactive CD4+ and CD8+ T cells infiltration in the islets, accompanied by invasive and rapid insulitis.
LAG-3 (CD223) is a cell surface molecule expressed on activated T cells, NK cells, B cells and plasmacytoid dendritic cells that plays an important but incompletely understood role in the function of these lymphocyte subsets. In addition, the interaction between LAG-3 and its major ligand, Class II MHC, is thought to play a role in modulating dendritic cell function. Recent preclinical studies have documented a role for LAG-3 in CD8 T cell exhaustion and blockade of the LAG-3/Class II interaction using a LAG-3 Ig fusion protein is being evaluated in a number of clinical trials in cancer patients.
This segment of the LAG-3-Next Generation Immunotherapy report encloses the detailed analysis of late-stage (Phase-III and Phase-II) pipeline drugs. It also helps to understand the indication-specific clinical trial details, expressive pharmacological actions, agreements and collaborations, approval and awards, advantages and disadvantages of each included drug, and the latest news and press releases.
The major key players such as MacroGenics/Zai Lab, Bristol-Myers Squibb/Ono Pharmaceuticals, Immutep, Novartis, Merck, F-star Therapeutics, Regeneron, Xencor, Incyte Biosciences/Agenus, Roche, GlaxoSmithKline, Innovent Biologics (Suzhou) Co. Ltd. and others will significantly increase the market during the forecast period (2022-2035).
The expected launch of emerging therapies, such as MGD013, Relatlimab, Eftilagimod Alpha (IMP321), LAG525, MK-4280, FS118, REGN3767, XmAb22841, INCAGN2385, RO7247669, TSR-033, IBI110 and other treatments, would lead to a significant increase in the market size during the forecast period (2022-2035).
MGD013 which is being developed by MacroGenics is an IgG4K bispecific DART molecule that binds to PD-1 and LAG-3 concomitantly or independently and disrupts non-redundant inhibitory pathways to restore shattered T-cell function further. The drug is the first in a series of product candidates that distinguish in the multiple immune regulatory targets. The drug is currently being evaluated in a phase II/III study in which the dose and schedule have been established and dose-expansion has been initiated in up to nine tumor types.
LAG525 (anti-LAG-3, also known as IMP701) which is under development by Novartis is an investigational immunotherapy being developed to potentially treat a range of solid tumors. The drug is a humanized form of IMP701 is currently being evaluated in five phase I and phase II clinical trials in combination with Novartis' PD-1 inhibitor spartalizumab for the treatment of various cancers.
Relatlimab (previously known as BMS-986016) is a cancer immunotherapy being developed by Bristol-Myers Squibb (BMS). The treatment has already shown benefit in melanoma patients and is also being tested in other cancers. Immunotherapies use the body's own immune system to fight cancer, instead of directly attacking cancer cells.
Eftilagimod alpha (IMP321), a soluble dimeric recombinant form of LAG-3, is a first-in-class antigen presenting cell activator under clinical development. By stimulating dendritic cells through MHC class II molecules, IMP321 was proven to induce sustained immune responses. Combining active immunotherapy with a standard cytotoxic chemotherapy regimen represents a promising novel strategy that might lead to therapeutic improvements in metastatic breast cancer.
A humanized, immunoglobulin G4 (IgG4) monoclonal antibody (MAb) directed against the inhibitory receptor lymphocyte activation gene-3 protein (LAG3), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-LAG3 monoclonal antibody MK-4280 binds to LAG3 expressed on tumor-infiltrating lymphocytes (TILs) and blocks its binding with major histocompatibility complex (MHC) class II molecules expressed on tumor cells. This activates antigen-specific T lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG3, a member of the immunoglobulin superfamily (IgSF), is expressed on various immune cells, and negatively regulates both proliferation and activation of T cells. Its expression on TILs is associated with tumor-mediated immune suppression.
The LAG-3-Next Generation Immunotherapy market outlook helps to cultivate a detailed comprehension of the historical, current and forecasted market trends by analyzing the market, unmet needs, drivers and barriers, and demand for better technology.
This segment gives a thorough detail of LAG-3-Next Generation Immunotherapy market trend of each late-stage pipeline therapy by evaluating their impact based on the annual cost of treatment, inclusion and exclusion criteria's, mechanism of action, compliance rate, growing need of the market, increasing patient pool, covered patient segment, expected launch year, competition with other therapies, brand value, their impact on the market, and view of the key opinion leaders. The calculated market data are presented with relevant tables and graphs to give a clear picture of the market at first sight.
According to DelveInsight, the LAG-3-Next Generation Immunotherapy market is expected to generate USD 3,421 Million in the year 2035 with a significant CAGR in the forecast period (2022-2035).
To keep up with current market trends, we take KOLs and SME's opinion working for third-generation immunotherapies in various indications through primary research to fill the data gaps and validate our secondary research. Their opinion helps us to understand and verify current and emerging therapies treatment patterns or current market trends. It will also support the clients in potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.
We perform Competitive and Market Intelligence analysis of the LAG-3-Next Generation Immunotherapy market by using various Competitive Intelligence tools that include - SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies, etc. The inclusion of the analysis entirely depends upon the availability of the data.