TIM-3:下一代免疫療法 - 競爭情形與市場預測 (2035年)
TIM-3-Next Generation Immunotherapy - Competitive Landscape and Market Forecast - 2035
本報告以全球主要7個國家的下一代型的癌症免疫治療藥的一種，TIM-3 (T細胞免疫球蛋白、粘蛋白網域-3) 為焦點，提供主要7個國家(7MM:美國，歐洲 (法國、德國、義大利、西班牙、英國) 、日本) 的臨床實驗的發展情形，及主要企業的開發中產品的概要，今後的市場規模趨勢預測 (2022∼2035年) 等調查。超時候做著
DelveInsight's 'TIM-3-Next Generation Immunotherapy-Competitive Landscape and Market Forecast-2035' report delivers an in-depth understanding of the TIM-3 as well as the market trends of TIM-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 TIM-3-Next Generation Immunotherapy from 2022 to 2035 segmented by seven major markets. This report discusses the recent findings on TIM-3, the role it plays in regulating immune responses in different cell types and the rationale for targeting TIM-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.
TIM-3 is a co-inhibitory receptor that is expressed on IFN-γ-producing T cells, FoxP3+ Treg cells and innate immune cells (macrophages and dendritic cells) where it has been shown to suppress their responses upon interaction with their ligand(s). TIM-3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that in vivo blockade of TIM-3 with other check-point inhibitors enhances anti-tumor immunity and suppresses tumor growth in several preclinical tumor models.
TIM-3, as a negative regulatory immune checkpoint, is detected in different types of immune cells, including T cells, regulatory T cells (Tregs), dendritic cells (DCs), B cells, macrophages, nature killer (NK) cells, and mast cells. TIM-3 is a type I membrane protein and consists of 281 amino acids. It comprises an extracellular domain, a single transmembrane domain, and a C-terminal cytoplasmic tail.
TIM-3 has four ligands, including galectin-9 (Gal-9), carcinoembryonic antigen cell adhesion molecule 1 (CEACAM-1), high-mobility group protein B1 (HMGB1), and phosphatidylserine (PS). Gal-9 was the first to be identified. It is a carbohydrate binding protein, specifically recognizing the structure of N-linked sugar chains in the TIM-3 immunoglobulin variable (IgV) domain. TIM-3/Gal-9 can inhibit cancer immunity by negatively regulating T-cell immunity. The connection of the TIM-3 IgV domain with Gal-9 can terminate T helper 1 (Th1) immune responses.
In the absence of ligand-mediated Tim-3 signaling, the Tyr 256 and Tyr 263 in the C-terminal tail of Tim-3 bind to Bat3. In this state, Bat3 recruits the catalytically active form of Lck, thereby forming an intracellular molecular complex with Tim-3 that preserves and potentially promotes T cell signaling and represses Tim-3-mediated cell death and exhaustion.
Interactions between Tim-3 ligands (Galectin 9), and Tim-3 leads to phosphorylation of Tyr 256 and Tyr 263 and release of Bat-3 from the Tim-3 tail, thereby promoting Tim-3-mediated T cell inhibition by allowing binding of SH2 domain-containing Src kinases (Lck/Fyn/Other proteins) and subsequent regulation of TCR signaling. Because Fyn and Bat3 bind to the same domain in the Tim-3 cytoplasmic tail, a likely molecular switch between Tim-3-Bat3 and Tim-3-Fyn probably triggers the switch of Tim-3 function from being permissive to TCR signaling to inhibition of proximal TCR signaling.
Combined use of antagonistic anti-TIM-3 antibodies with agonistic antibodies to pro-stimulatory molecules on tumor-specific T cells, such as CD137, has demonstrated long-term protection in a murine model of ovarian cancer. This therapeutic regimen of using Tim-3 blockade with activation of a pro-stimulatory molecule on T cells could be exploited in the future to obtain objective anti-tumor responses in patients. One could expect that further exploratory studies would reveal additional exciting anti-TIM-3 immunotherapeutic approaches to treat cancers.
Targeting TIM-3 along with other checkpoint inhibitors or combining TIM-3 inhibition with new immunotherapeutic approaches that activate cancer-specific T-cell stimulatory molecules has high potential for developing modalities with durable clinical benefit. In addition, TIM-3 blockade may also induce an anti-tumor immune response and mediate tumor regression in situations where anti-PD-1 or anti-CTLA4 does not work, such as in colorectal carcinomas. The key challenge in moving forward is to develop reliable strategies and indications under which combination therapies should be tested. Given the fact that PD-1 blockade may lead to upregulation of TIM-3, blockade of TIM-3 following development of adaptive resistance to PD-1 or other checkpoint inhibitors holds promise in developing combination therapies in which anti- TIM-3 is a key component.
This segment of the TIM-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 Symphogen, GlaxoSmithKline, Novartis, Bristol-Myers Squibb/ Ono Pharmaceuticals, BeiGene, Incyte Biosciences/Agenus, Roche, Eli Lilly and many others will significantly increase the market during the forecast period (2022-2035).
The expected launch of emerging therapies, such as TSR-022, MBG453, ONO-7807/BMS-986258, BGB-A425 +/- Tislelizumab, Sym023, INCAGN2390, RG7769/RO7121661, LY3321367, Sym022 and other treatments, would lead to a significant increase in the market size during the forecast period (2022-2035).
Sym023 is a mAb that binds TIM3 and induces activation of immune cells. Currently, Sym023 (targeting TIM3) is being investigated in Phase 1 trials in combination with Sym021 (targeting PD1) and as single antibody. TIM3 and PD1 are immune checkpoints playing important roles in regulating immune responses, including the body's immune response to tumor cells.
TSR-022 is an investigational drug that is under development by GlaxoSmithKline. Initially, Tesaro is developing this drug for the treatment of various tumors. This drug is currently under phase II development for the treatment of melanoma stage III, melanoma Stage IV, adult primary liver cancer, advanced adult primary liver cancer, and localized unresectable adult primary liver cancer.
MBG453 is an immunotherapy that Novartis is developing to treat solid tumors and hematologic cancers, which form in the blood or immune system. MBG453 inhibits TIM-3, a protein found on the surface of certain immune T-cells. Its full scientific name is T-cell immunoglobulin and mucin-domain-containing-3. MBG453 binds to TIM-3 on the surface of T-cells, releasing the brakes that the tumor applied to the immune system. This allows it to function normally against cancer cells, reducing tumor growth.
Novartis is conducting Phase 1/2 clinical trials of MBB453 as a treatment for several types of cancer.
An antibody against the inhibitory T-cell receptor T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; TIM3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immune checkpoint inhibitory and antineoplastic activities. Following administration, anti-TIM-3 antibody BMS-986258 binds to TIM-3 that is expressed on certain T cells, including tumor infiltrating lymphocytes (TILs). This abrogates T-cell inhibition, activates antigen-specific T lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which together result in decreased tumor growth. TIM-3, a transmembrane protein and immune checkpoint receptor, is associated with tumor-mediated immune suppression.
LY3321367 mAb targets TIM-3 on immune cells and LY3300054 mAb targets PD-L1 on tumor cells and tumor-infiltrating immune cells. According to the clinical trial results, LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The [dose-limiting toxicity] for LY3321367 combination therapy is 1,200-mg intravenous infusions [once every 2 weeks] for cycles 1-2; 600-mg infusions [once every 2 weeks] starting at cycle 3 onward."
The TIM-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 TIM-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 TIM-3-Next Generation Immunotherapy market is expected to generate USD 1,218 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 TIM-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.