New Study on Tumor Immunotherapy: Near-Infrared Light Immunotherapy Drugs

the development of cancer drugs has been one of the most important goals in the field of drug research and development, for tumor physiological mechanism of different links, researchers have issued a lot of effective drugs, many related drugs have been listed and achieved good sales results But there are still a large number of drugs under study in the clinical or preclinical stage, many of which are designed with whimsy ideas, and near-infrared photoimmunotherapy (NIR-PIT) drugs are one of them Near-infrared photoimmunotherapy (NIR-PIT) drugs are generally composed of specific monoantigens (mAb) that target tumor and photoabsorbr (photoaborber) connected by a connecting agent (linker), which is essentially an ADC (antibody-linked drug) drug The specific monoantigen function of NIR-PIT drug mechanism near-infrared photoimmunorapy (NIR-PIT) drug is the same as that of general ADC drugs, and is specifically targeted to tumor surface-related targets However, unlike conventional ADC drugs, the chemical small molecule salutation salutation salutation connected to a specific monoantigen through a connector (linker) is not a cytotoxic substance, but a water-soluble pyride stoic derivative (as described below is as the ass of ASP-1929's silicone ithane derivative IR700 (IRDye700DX) Ir700 is a small molecule that can be activated by light excited by near-infrared light In the body, near-infrared light immunotherapy (NIR-PIT) drugs accurately target tumor surface targets with specific monoantigens, while bringing the IR700 connected to them to the tumor microenvironment When near-infrared light is used, near-infrared light causes an axial ligand release reaction, which significantly alters the hydrophilic properties of IR700, resulting in a change in the shape of the conjugate and its tendency to gather, a physical change that induces physical stress in the cell membrane of the tumor , resulting in increased transmembrane water flow, eventually leading to cell rupture and necrosis cell death Of course, this is only the first step in the death of tumor cells, a process that kills tumor cells, which, unlike conventional ADC drugs, are not known as photoimmunotherapy In this design, the IR700 was chosen as a photoabsorbr (photoaborber) because it can be excited by near-infrared light, which is non-ionized, will not cause damage to DNA, harmless to normal cells, and near-infrared light can penetrate tissue several centimeters Because near-infrared photoimmunotherapy (NIR-PIT) drugs mainly bind to tumor cells that over-express tumor-related antigens, photoactivated conjugated drugs selectively kill tumor cells without damaging adjacent normal cells, including tumor-soaked immune cells In addition, the IR700 itself is a water-soluble photo dye, which is not phototoxic or biotoxic Therefore, the uncombined IR700 that is dissohned from the NIR-PIT drug is safe and easily excreted from the urine Target-specific NIR-PIT drugs combined with limited near-infrared exposure can form highly targeted tumor treatment, which has minimal or no damage to normal tissue This theory has been confirmed in the early results of phase 1/2 clinical trial It is worth noting that, unlike other traditional therapies, the death of highly specific tumor cells induced by NIR-PIT drugs does not impair the body's immunity to tumors and may even activate a polyclonal tumor-specific immune response In fact, the nature of NIR-PIT drugs that cause rapid cell death makes them highly immunogenic NIR-PIT drugs, when cells break down and die, rapidly release specific antigens associated with tumors in cells, which inducelocal dendritic cells to activate, which in turn activates T cells, leading to T-cell proliferation and the of their mediate
d tumors cell killing, a process known as immunogenic cell death (immunogenic, death ICD) The above immunogenic cell death (ICD), caused by NIR-PIT drugs, is the second step in killing tumor cells, and is also the origin of photoimmunothesis The fastest-growing nIR-PIT drug in research on near-infrared light immunotherapy (NIR-PIT) drugs under study is AsP-1929 (also known as RM-1929) of Rakuten Medical ASP-1929 is a conjugated drug made up of citoxianosanda and IR700 connected by a linker Citoxiaim is a chimeric IgG1 monoclonal antibody, approved by the U.S FDA in 2004, its molecular target is epidermal growth factor receptor (EGFR) EGFR is expressed in a variety of types of solid tumors, including head and neck cancer, esophageal cancer, lung cancer, colorectal cancer, pancreatic cancer and other cancers Currently, asP-1929 clinical trials are mainly focused on head and neck cancer, so far there are a number of clinical trials for head and neck cancer closed or in progress There are currently two Phase III clinical cases available on ClinicalTrial.gov One phase
III clinical trial for the treatment of head and neck cancer in ASP-1929, , and the other was a recently registered Phase Ii study with PD-1 mono-anti-Pembrozumab or Cemiplimab Data from the RM-1929/101 study (NCT02422979) have been disclosed This is a phase IIa clinical study of patients with recurrent head and neck cancer who cannot be treated with surgery, radiotherapy or platinum chemotherapy, with a total of 30 patients included by the date of publication of the data No dose-limiting toxicity or skin photosensitive reactions were observed in the study, and SAE, which may be associated with the study of treatment, had pain, tumors
bleeding and swelling The objective mitigation rate (ORR) was 28% (8/28) and the full mitigation rate (CR) was 14% (4/28) Median progression life (mPFS) in 28 assessable patients was 173 days (5.7 months) and the median total survival time (mOS) for the entire 30 patients was 278 days (9.1 months) The results showed that the patient's photoimmunorapy with RM1929 was safe and well tolerated Based on the above data, the U.S FDA granted ASP-1929 fast-track eligibility In addition, ASP-1929 has been recognized in Japan by the Ministry of Health, Labour and Welfare of Japan as being certified as receiving priority consulting services and regulatory authorization review for designated drugs In addition to ASP-1929, there are two NIR-PIT drugs under development, according to the Rakuten Medical website According to information disclosed on its official website, one of the drugs was CD25 mono-anti-conconjugate NIR-PIT (anti-CD25-IR700conjugate), which in preclinical studies showed good anti-
tumor effects in animal models of advanced tumors In addition, in addition to Rakuten Medical, a number of other companies or research institutions have developed NIR-PIT drugs, but are in a relatively early stage, including 131I (PcMAb) (CD38 mono-anti-conjoined NIR-PIT drugs), AvIR-mediated PIT, Anti-TFbody1849-ICGconjugate, Avelumab-IR700, etc Conclusion Near-Infrared Light Immunotherapy (NIR-PIT) drugs can overcome problems with traditional antibody-based therapy, including inequality or deficiency of antibodies or ADCs, as well as tumor heterogeneity Because the NIR-PIT drug-induced polyclonal immune response can eliminate tumor cells that survive the first step of NIR-PIT drug killing, even if the NIR-PIT drug is insufficient due to uneven expression of the target antigen, or is unevenly delivered or insufficient in dose, the subsequent second step polyclonal immune response will kill the residual tumor cells In addition, near-infrared photo immunotherapy (NIR-PIT) drugs can also be used as a pre-existing PD-1 monoantigen, PD-L1 monoantigen or CTLA-4 monoantigen treatment, enhance their tumor immune response There is currently little development of such drugs, relatively competitive immuno-checkpoint inhibitors, the development of near-infrared light immunotherapy (NIR-PIT) drugs may be a good choice (
Biological Valley Bioon.com)